Affective and Cognitive Impairments in Rodent Models of Diabetes

Enza      Palazzo; Ida      Marabese; Serena      Boccella; Carmela      Belardo; Gorizio      Pierretti; Sabatino      Maione
Abstract

Diabetes and related acute and long-term complications have a profound impact on cognitive, emotional, and social behavior, suggesting that the central nervous system (CNS) is a crucial substrate for diabetic complications. When anxiety, depression, and cognitive deficits occur in diabetic patients, the symptoms and complications related to the disease worsen, contributing to lower quality of life while increasing health care costs and mortality. Experimental models of diabetes in rodents are a fundamental and valuable tool for improving our understanding of the mechanisms underlying the close and reciprocal link between diabetes and CNS alterations, including the development of affective and cognitive disorders. Such models must reproduce the different components of this pathological condition in humans and, therefore, must be associated with affective and cognitive behavioral alterations. Beyond tight glycemic control, there are currently no specific therapies for neuropsychiatric comorbidities associated with diabetes; animal models are, therefore, essential for the development of adequate therapies. To our knowledge, there is currently no review article that summarizes changes in affective and cognitive behavior in the most common models of diabetes in rodents. Therefore, in this review, we have reported the main evidence on the alterations of affective and cognitive behavior in the different models of diabetes in rodents, the main mechanisms underlying these comorbidities, and the applicable therapeutic strategy.
Graphical Abstract

[1]
Lovic, D.; Piperidou, A.; Zografou, I.; Grassos, H.; Pittaras, A.; Manolis, A. The growing epidemic of diabetes mellitus. Curr. Vasc. Pharmacol.,  2020, 18(2), 104-109.
 [http://dx.doi.org/10.2174/1570161117666190405165911] [PMID: 30961501]

[2]
Mooradian, A.D. Pathophysiology of central nervous system complications in diabetes mellitus. Clin. Neurosci.,  1997, 4(6), 322-326.
 [PMID: 9358975]

[3]
Gaspar, J.M.; Baptista, F.I.; Macedo, M.P.; Ambrósio, A.F. Inside the diabetic brain: Role of different players involved in cognitive decline. ACS Chem. Neurosci.,  2016, 7(2), 131-142.
 [http://dx.doi.org/10.1021/acschemneuro.5b00240] [PMID: 26667832]

[4]
Martin, H.; Bullich, S.; Guiard, B.P.; Fioramonti, X. The impact of insulin on the serotonergic system and consequences on diabetes‐associated mood disorders. J. Neuroendocrinol.,  2021, 33(4), e12928.
 [http://dx.doi.org/10.1111/jne.12928] [PMID: 33506507]

[5]
Asslih, S.; Damri, O.; Agam, G. Neuroinflammation as a common denominator of complex diseases (Cancer, Diabetes Type 2, and Neuropsychiatric Disorders). Int. J. Mol. Sci.,  2021, 22(11), 6138.
 [http://dx.doi.org/10.3390/ijms22116138] [PMID: 34200240]

[6]
Anderson, R.J.; Freedland, K.E.; Clouse, R.E.; Lustman, P.J. The prevalence of comorbid depression in adults with diabetes: A meta-analysis. Diabetes Care,  2001, 24(6), 1069-1078.
 [http://dx.doi.org/10.2337/diacare.24.6.1069] [PMID: 11375373]

[7]
Harding, K.A.; Pushpanathan, M.E.; Whitworth, S.R.; Nanthakumar, S.; Bucks, R.S.; Skinner, T.C. Depression prevalence in Type 2 diabetes is not related to diabetes–depression symptom overlap but is related to symptom dimensions within patient self‐report measures: A meta‐analysis. Diabet. Med.,  2019, 36(12), 1600-1611.
 [http://dx.doi.org/10.1111/dme.14139] [PMID: 31532013]

[8]
Farooqi, A.; Gillies, C.; Sathanapally, H.; Abner, S.; Seidu, S.; Davies, M.J.; Polonsky, W.H.; Khunti, K. A systematic review and meta-analysis to compare the prevalence of depression between people with and without Type 1 and Type 2 diabetes. Prim. Care Diabetes,  2022, 16(1), 1-10.
 [http://dx.doi.org/10.1016/j.pcd.2021.11.001] [PMID: 34810141]

[9]
Roy, T.; Lloyd, C.E. Epidemiology of depression and diabetes: A systematic review. J. Affect. Disord.,  2012, 142, S8-S21.
 [http://dx.doi.org/10.1016/S0165-0327(12)70004-6] [PMID: 23062861]

[10]
Tomic, D.; Shaw, J.E.; Magliano, D.J. The burden and risks of emerging complications of diabetes mellitus. Nat. Rev. Endocrinol.,  2022, 18(9), 525-539.
 [http://dx.doi.org/10.1038/s41574-022-00690-7] [PMID: 35668219]

[11]
Katon, W.; Von Korff, M.; Ciechanowski, P.; Russo, J.; Lin, E.; Simon, G.; Ludman, E.; Walker, E.; Bush, T.; Young, B. Behavioral and clinical factors associated with depression among individuals with diabetes. Diabetes Care,  2004, 27(4), 914-920.
 [http://dx.doi.org/10.2337/diacare.27.4.914] [PMID: 15047648]

[12]
Sartorius, N. Depression and diabetes. Dialogues Clin. Neurosci.,  2018, 20(1), 47-52.
 [http://dx.doi.org/10.31887/DCNS.2018.20.1/nsartorius] [PMID: 29946211]

[13]
Aftab, A.; Bhat, C.; Gunzler, D.; Cassidy, K.; Thomas, C.; McCormick, R.; Dawson, N.V.; Sajatovic, M. Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial. Int. J. Psychiatry Med.,  2018, 53(3), 126-140.
 [http://dx.doi.org/10.1177/0091217417749795] [PMID: 29280685]

[14]
Boden, M.T. Prevalence of mental disorders and related functioning and treatment engagement among people with diabetes. J. Psychosom. Res.,  2018, 106, 62-69.
 [http://dx.doi.org/10.1016/j.jpsychores.2018.01.001] [PMID: 29455901]

[15]
Latas, M.; Vučinić, L.D.; Spasić, S.M. Anxiety disorders and medical illness comorbidity and treatment implications. Curr. Opin. Psychiatry,  2019, 32(5), 429-434.
 [http://dx.doi.org/10.1097/YCO.0000000000000527] [PMID: 31116127]

[16]
Ryan, J.P.; Fine, D.F.; Rosano, C. Type 2 diabetes and cognitive impairment: Contributions from neuroimaging. J. Geriatr. Psychiatry Neurol.,  2014, 27(1), 47-55.
 [http://dx.doi.org/10.1177/0891988713516543] [PMID: 24394151]

[17]
Koekkoek, P.S.; Kappelle, L.J.; van den Berg, E.; Rutten, G.E.H.M.; Biessels, G.J. Cognitive function in patients with diabetes mellitus: Guidance for daily care. Lancet Neurol.,  2015, 14(3), 329-340.
 [http://dx.doi.org/10.1016/S1474-4422(14)70249-2] [PMID: 25728442]

[18]
Rees, D.A.; Alcolado, J.C. Animal models of diabetes mellitus. Diabet. Med.,  2005, 22(4), 359-370.
 [http://dx.doi.org/10.1111/j.1464-5491.2005.01499.x] [PMID: 15787657]

[19]
Al-awar, A.; Kupai, K.; Veszelka, M.; Szűcs, G.; Attieh, Z.; Murlasits, Z.; Török, S.; Pósa, A.; Varga, C. Experimental diabetes mellitus in different animal models. J. Diabetes Res.,  2016, 2016, 1-12.
 [http://dx.doi.org/10.1155/2016/9051426] [PMID: 27595114]

[20]
Pandey, S.; Dvorakova, M.C. Future perspective of diabetic animal models. Endocr. Metab. Immune Disord. Drug Targets,  2020, 20(1), 25-38.
 [http://dx.doi.org/10.2174/1871530319666190626143832] [PMID: 31241444]

[21]
Herder, C.; Schmitt, A.; Budden, F.; Reimer, A.; Kulzer, B.; Roden, M.; Haak, T.; Hermanns, N. Association between pro- and anti-inflammatory cytokines and depressive symptoms in patients with diabetes-potential differences by diabetes type and depression scores. Transl. Psychiatry,  2018, 7(11), 1.
 [http://dx.doi.org/10.1038/s41398-017-0009-2] [PMID: 29520075]

[22]
Bąk, E.; Marcisz-Dyla, E.; Młynarska, A.; Sternal, D.; Kadłubowska, M.; Marcisz, C. Prevalence of depressive symptoms in patients with type 1 and 2 diabetes mellitus. Patient Prefer. Adherence,  2020, 14, 443-454.
 [http://dx.doi.org/10.2147/PPA.S237767] [PMID: 32184573]

[23]
Réus, G.Z.; Carlessi, A.S.; Silva, R.H.; Ceretta, L.B.; Quevedo, J. Relationship of oxidative stress as a link between diabetes mellitus and major depressive disorder. Oxid. Med. Cell. Longev.,  2019, 2019, 1-6.
 [http://dx.doi.org/10.1155/2019/8637970] [PMID: 30944699]

[24]
Ceretta, L.B.; Réus, G.Z.; Stringari, R.B.; Ribeiro, K.F.; Zappellini, G.; Aguiar, B.W.; Pfaffenseller, B.; Lersh, C.; Kapczinski, F.; Quevedo, J. Imipramine treatment reverses depressive-like behavior in alloxan-diabetic rats. Diabetes Metab. Res. Rev.,  2012, 28(2), 139-144.
 [http://dx.doi.org/10.1002/dmrr.1285] [PMID: 22423384]

[25]
Tang, Z.J.; Zou, W.; Yuan, J.; Zhang, P.; Tian, Y.; Xiao, Z.F.; Li, M.H.; Wei, H.J.; Tang, X.Q. Antidepressant-like and anxiolytic-like effects of hydrogen sulfide in streptozotocin-induced diabetic rats through inhibition of hippocampal oxidative stress. Behav. Pharmacol.,  2015, 26(5), 427-435.
 [http://dx.doi.org/10.1097/FBP.0000000000000143] [PMID: 25932716]

[26]
Miyata, S.; Hirano, S.; Kamei, J. Diabetes attenuates the antidepressant-like effect mediated by the activation of 5-HT1A receptor in the mouse tail suspension test. Neuropsychopharmacology,  2004, 29(3), 461-469.
 [http://dx.doi.org/10.1038/sj.npp.1300354] [PMID: 14628002]

[27]
Huang, C.W.; Hong, T.W.; Wang, Y.J.; Chen, K.C.; Pei, J.C.; Chuang, T.Y.; Lai, W.S.; Tsai, S.H.; Chu, R.; Chen, W.C.; Sheen, L.Y.; Takahashi, S.; Ding, S.T.; Shen, T.L. Ophiocordyceps formosana improves hyperglycemia and depression-like behavior in an STZ-induced diabetic mouse model. BMC Complement. Altern. Med.,  2016, 16(1), 310.
 [http://dx.doi.org/10.1186/s12906-016-1278-7] [PMID: 27553852]

[28]
Miyata, S.; Yamada, N.; Hirano, S.; Tanaka, S.; Kamei, J. Diabetes attenuates psychological stress-elicited 5-HT secretion in the prefrontal cortex but not in the amygdala of mice. Brain Res.,  2007, 1147, 233-239.
 [http://dx.doi.org/10.1016/j.brainres.2007.02.001] [PMID: 17320057]

[29]
Youssef, D.A.; El-Fayoumi, H.M.; Mahmoud, M.F. Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-γ receptors. Biomed. Pharmacother.,  2019, 110, 145-154.
 [http://dx.doi.org/10.1016/j.biopha.2018.11.039] [PMID: 30469079]

[30]
Dutheil, S.; Ota, K.T.; Wohleb, E.S.; Rasmussen, K.; Duman, R.S. High-fat diet induced anxiety and anhedonia: Impact on brain homeostasis and inflammation. Neuropsychopharmacology,  2016, 41(7), 1874-1887.
 [http://dx.doi.org/10.1038/npp.2015.357] [PMID: 26658303]

[31]
Hassan, A.M.; Mancano, G.; Kashofer, K.; Fröhlich, E.E.; Matak, A.; Mayerhofer, R.; Reichmann, F.; Olivares, M.; Neyrinck, A.M.; Delzenne, N.M.; Claus, S.P.; Holzer, P. High-fat diet induces depression-like behaviour in mice associated with changes in microbiome, neuropeptide Y, and brain metabolome. Nutr. Neurosci.,  2019, 22(12), 877-893.
 [http://dx.doi.org/10.1080/1028415X.2018.1465713] [PMID: 29697017]

[32]
Sharma, A.N.; Elased, K.M.; Garrett, T.L.; Lucot, J.B. Neurobehavioral deficits in db/db diabetic mice. Physiol. Behav.,  2010, 101(3), 381-388.
 [http://dx.doi.org/10.1016/j.physbeh.2010.07.002] [PMID: 20637218]

[33]
Dinel, A.L.; André, C.; Aubert, A.; Ferreira, G.; Layé, S.; Castanon, N. Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome. PLoS One,  2011, 6(9), e24325.
 [http://dx.doi.org/10.1371/journal.pone.0024325] [PMID: 21949705]

[34]
Li, S.; Zhai, X.; Rong, P.; McCabe, M.F.; Wang, X.; Zhao, J.; Ben, H.; Wang, S. Therapeutic effect of vagus nerve stimulation on depressive-like behavior, hyperglycemia and insulin receptor expression in Zucker fatty rats. PLoS One,  2014, 9(11), e112066.
 [http://dx.doi.org/10.1371/journal.pone.0112066] [PMID: 25365428]

[35]
Pan, Y.; Hong, Y.; Zhang, Q.Y.; Kong, L.D. Impaired hypothalamic insulin signaling in CUMS rats: Restored by icariin and fluoxetine through inhibiting CRF system. Psychoneuroendocrinology,  2013, 38(1), 122-134.
 [http://dx.doi.org/10.1016/j.psyneuen.2012.05.007] [PMID: 22663897]

[36]
Tsuneki, H.; Tokai, E.; Sugawara, C.; Wada, T.; Sakurai, T.; Sasaoka, T. Hypothalamic orexin prevents hepatic insulin resistance induced by social defeat stress in mice. Neuropeptides,  2013, 47(3), 213-219.
 [http://dx.doi.org/10.1016/j.npep.2013.02.002] [PMID: 23510906]

[37]
Delanogare, E.; de Souza, R.M.; Rosa, G.K.; Guanabara, F.G.; Rafacho, A.; Moreira, E.L.G. Enriched environment ameliorates dexamethasone effects on emotional reactivity and metabolic parameters in mice. Stress,  2020, 23(4), 466-473.
 [http://dx.doi.org/10.1080/10253890.2020.1735344] [PMID: 32107952]

[38]
Sestile, C.C.; Maraschin, J.C.; Rangel, M.P.; Cuman, R.K.N.; Audi, E.A. Antidepressant-like effect of insulin in streptozotocin-induced type 2 diabetes mellitus rats. Basic Clin. Pharmacol. Toxicol.,  2016, 119(3), 243-248.
 [http://dx.doi.org/10.1111/bcpt.12563] [PMID: 26857652]

[39]
Kleinridders, A.; Cai, W.; Cappellucci, L.; Ghazarian, A.; Collins, W.R.; Vienberg, S.G.; Pothos, E.N.; Kahn, C.R. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. Proc. Natl. Acad. Sci.,  2015, 112(11), 3463-3468.
 [http://dx.doi.org/10.1073/pnas.1500877112] [PMID: 25733901]

[40]
Grillo, C.A.; Piroli, G.G.; Kaigler, K.F.; Wilson, S.P.; Wilson, M.A.; Reagan, L.P. Downregulation of hypothalamic insulin receptor expression elicits depressive-like behaviors in rats. Behav. Brain Res.,  2011, 222(1), 230-235.
 [http://dx.doi.org/10.1016/j.bbr.2011.03.052] [PMID: 21458499]

[41]
Grillo, C.A.; Piroli, G.G.; Lawrence, R.C.; Wrighten, S.A.; Green, A.J.; Wilson, S.P.; Sakai, R.R.; Kelly, S.J.; Wilson, M.A.; Mott, D.D.; Reagan, L.P. Hippocampal insulin resistance impairs spatial learning and synaptic plasticity. Diabetes,  2015, 64(11), 3927-3936.
 [http://dx.doi.org/10.2337/db15-0596] [PMID: 26216852]

[42]
Heni, M.; Hennige, A.M.; Peter, A.; Siegel-Axel, D.; Ordelheide, A.M.; Krebs, N.; Machicao, F.; Fritsche, A.; Häring, H.U.; Staiger, H. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS One,  2011, 6(6), e21594.
 [http://dx.doi.org/10.1371/journal.pone.0021594] [PMID: 21738722]

[43]
Cai, W.; Xue, C.; Sakaguchi, M.; Konishi, M.; Shirazian, A.; Ferris, H.A.; Li, M.E.; Yu, R.; Kleinridders, A.; Pothos, E.N.; Kahn, C.R. Insulin regulates astrocyte gliotransmission and modulates behavior. J. Clin. Invest.,  2018, 128(7), 2914-2926.
 [http://dx.doi.org/10.1172/JCI99366] [PMID: 29664737]

[44]
Ramos-Rodriguez, J.J.; Molina-Gil, S.; Ortiz-Barajas, O.; Jimenez-Palomares, M.; Perdomo, G.; Cozar-Castellano, I.; Lechuga-Sancho, A.M.; Garcia-Alloza, M. Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models. PLoS One,  2014, 9(2), e89229.
 [http://dx.doi.org/10.1371/journal.pone.0089229] [PMID: 24586614]

[45]
Murata, Y.; Narisawa, Y.; Shimono, R.; Ohmori, H.; Mori, M.; Ohe, K.; Mine, K.; Enjoji, M. A high fat diet-induced decrease in hippocampal newly-born neurons of male mice is exacerbated by mild psychological stress using a Communication Box. J. Affect. Disord.,  2017, 209, 209-216.
 [http://dx.doi.org/10.1016/j.jad.2016.11.046] [PMID: 27930914]

[46]
Nam, S.M.; Kim, J.W.; Kwon, H.J.; Yoo, D.Y.; Jung, H.Y.; Kim, D.W.; Hwang, I.K.; Seong, J.K.; Yoon, Y.S. Differential effects of low- and high-dose zinc supplementation on synaptic plasticity and neurogenesis in the hippocampus of control and high-fat diet-fed mice. Neurochem. Res.,  2017, 42(11), 3149-3159.
 [http://dx.doi.org/10.1007/s11064-017-2353-2] [PMID: 28770438]

[47]
Okuyama, S.; Shinoka, W.; Nakamura, K.; Kotani, M.; Sawamoto, A.; Sugawara, K.; Sudo, M.; Nakajima, M.; Furukawa, Y. Suppressive effects of the peel of Citrus kawachiensis (Kawachi Bankan) on astroglial activation, tau phosphorylation, and inhibition of neurogenesis in the hippocampus of type 2 diabetic db/db mice. Biosci. Biotechnol. Biochem.,  2018, 82(8), 1384-1395.
 [http://dx.doi.org/10.1080/09168451.2018.1469396] [PMID: 29732953]

[48]
Mayanil, C.S.K.; Kazmi, S.M.I.; Baquer, N.Z. Changes in monoamine oxidase activity in rat brain during alloxan diabetes. J. Neurochem.,  1982, 38(1), 179-183.
 [http://dx.doi.org/10.1111/j.1471-4159.1982.tb10869.x] [PMID: 7050304]

[49]
Ohtani, N.; Ohta, M.; Sugano, T. Microdialysis study of modification of hypothalamic neurotransmitters in streptozotocin-diabetic rats. J. Neurochem.,  1997, 69(4), 1622-1628.
 [http://dx.doi.org/10.1046/j.1471-4159.1997.69041622.x] [PMID: 9326291]

[50]
Sandrini, M.; Vitale, G.; Vergoni, A.V.; Ottani, A.; Bertolini, A. Streptozotocin-induced diabetes provokes changes in serotonin concentration and on 5-HT1A and 5-HT2 receptors in the rat brain. Life Sci.,  1997, 60(16), 1393-1397.
 [http://dx.doi.org/10.1016/S0024-3205(97)00084-2] [PMID: 9096260]

[51]
Barber, M.; Kasturi, B.S.; Austin, M.E.; Patel, K.P. MohanKumar, S.M.J.; MohanKumar, P.S. Diabetes-induced neuroendocrine changes in rats: Role of brain monoamines, insulin and leptin. Brain Res.,  2003, 964(1), 128-135.
 [http://dx.doi.org/10.1016/S0006-8993(02)04091-X] [PMID: 12573521]

[52]
Yamato, T.; Misumi, Y.; Yamasaki, S.; Kino, M.; Aomine, M. Diabetes mellitus decreases hippocampal release of neurotransmitters: An in vivo microdialysis study of awake, freely moving rats. Diabetes Nutr. Metab.,  2004, 17(3), 128-136.
 [PMID: 15334789]

[53]
Abraham, P.M.; Paul, J.; Paulose, C.S. Down regulation of cerebellar serotonergic receptors in streptozotocin induced diabetic rats: Effect of pyridoxine and Aegle marmelose. Brain Res. Bull.,  2010, 82(1-2), 87-94.
 [http://dx.doi.org/10.1016/j.brainresbull.2010.02.005] [PMID: 20170713]

[54]
Gupta, D.; Kurhe, Y.; Radhakrishnan, M. Antidepressant effects of insulin in streptozotocin induced diabetic mice: Modulation of brain serotonin system. Physiol. Behav.,  2014, 129, 73-78.
 [http://dx.doi.org/10.1016/j.physbeh.2014.02.036] [PMID: 24582678]

[55]
Petrišić, M.Š.; Augood, S.J.; Bicknell, R.J. Monoamine transporter gene expression in the central nervous system in diabetes mellitus. J. Neurochem.,  1997, 68(6), 2435-2441.
 [http://dx.doi.org/10.1046/j.1471-4159.1997.68062435.x] [PMID: 9166737]

[56]
Zemdegs, J.; Quesseveur, G.; Jarriault, D.; Pénicaud, L.; Fioramonti, X.; Guiard, B.P. High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice. Br. J. Pharmacol.,  2016, 173(13), 2095-2110.
 [http://dx.doi.org/10.1111/bph.13343] [PMID: 26472268]

[57]
Zemdegs, J.; Martin, H.; Pintana, H.; Bullich, S.; Manta, S.; Marqués, M.A.; Moro, C.; Layé, S.; Ducrocq, F.; Chattipakorn, N.; Chattipakorn, S.C.; Rampon, C.; Pénicaud, L.; Fioramonti, X.; Guiard, B.P. Metformin promotes anxiolytic and antidepressant-like responses in insulin-resistant mice by decreasing circulating branched-chain amino acids. J. Neurosci.,  2019, 39(30), 5935-5948.
 [http://dx.doi.org/10.1523/JNEUROSCI.2904-18.2019] [PMID: 31160539]

[58]
Fernstrom, J.D. Large neutral amino acids: Dietary effects on brain neurochemistry and function. Amino Acids,  2013, 45(3), 419-430.
 [http://dx.doi.org/10.1007/s00726-012-1330-y] [PMID: 22677921]

[59]
Balali Dehkordi, S.; Sajedianfard, J.; Owji, A.A. The effect of intra-cerebroventricular injection of insulin on the levels of monoamines on the raphe magnus nucleus of non-diabetic and short-term diabetic rats in the formalin test. Iran. J. Basic Med. Sci.,  2019, 22(8), 915-921.
 [PMID: 31579448]

[60]
Soliman, E.; Essmat, N.; Mahmoud, M.F.; Mahmoud, A.A.A. Impact of some oral hypoglycemic agents on type 2 diabetes-associated depression and reserpine-induced depression in rats: the role of brain oxidative stress and inflammation. Naunyn Schmiedebergs Arch. Pharmacol.,  2020, 393(8), 1391-1404.
 [http://dx.doi.org/10.1007/s00210-020-01838-w] [PMID: 32077986]

[61]
Essmat, N.; Soliman, E.; Mahmoud, M.F.; Mahmoud, A.A.A. Antidepressant activity of anti-hyperglycemic agents in experimental models: A review. Diabetes Metab. Syndr.,  2020, 14(5), 1179-1186.
 [http://dx.doi.org/10.1016/j.dsx.2020.06.021] [PMID: 32673838]

[62]
Barnard, K.; Peveler, R.C.; Holt, R.I.G. Antidepressant medication as a risk factor for type 2 diabetes and impaired glucose regulation: Systematic review. Diabetes Care,  2013, 36(10), 3337-3345.
 [http://dx.doi.org/10.2337/dc13-0560] [PMID: 24065841]

[63]
Bhattacharjee, S.; Bhattacharya, R.; Kelley, G.A.; Sambamoorthi, U. Antidepressant use and new-onset diabetes: A systematic review and meta-analysis. Diabetes Metab. Res. Rev.,  2013, 29(4), 273-284.
 [http://dx.doi.org/10.1002/dmrr.2393] [PMID: 23390036]

[64]
Salvi, V.; Grua, I.; Cerveri, G.; Mencacci, C.; Barone-Adesi, F. The risk of new-onset diabetes in antidepressant users - A systematic review and meta-analysis. PLoS One,  2017, 12(7), e0182088.
 [http://dx.doi.org/10.1371/journal.pone.0182088] [PMID: 28759599]

[65]
Potter van Loon, B.J.; Radder, J.K.; Frölich, M.; Krans, H.M.; Zwinderman, A.H.; Meinders, A.E. Fluoxetine increases insulin action in obese nondiabetic and in obese non-insulin-dependent diabetic individuals. Int. J. Obes. Relat. Metab. Disord.,  1992, 16(2), 79-85.
 [PMID: 1316330]

[66]
Maheux, P.; Ducros, F.; Bourque, J.; Garon, J.; Chiasson, J-L. Fluoxetine improves insulin sensitivity in obese patients with non-insulin-dependent diabetes mellitus independently of weight loss. Int. J. Obes.,  1997, 21(2), 97-102.
 [http://dx.doi.org/10.1038/sj.ijo.0800372] [PMID: 9043962]

[67]
McIntyre, R.S.; Soczynska, J.K.; Konarski, J.Z.; Kennedy, S.H. The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms. Expert Opin. Drug Saf.,  2006, 5(1), 157-168.
 [http://dx.doi.org/10.1517/14740338.5.1.157] [PMID: 16370964]

[68]
Brieler, J.A.; Lustman, P.J.; Scherrer, J.F.; Salas, J.; Schneider, F.D. Antidepressant medication use and glycaemic control in co-morbid type 2 diabetes and depression. Fam. Pract.,  2016, 33(1), 30-36.
 [http://dx.doi.org/10.1093/fampra/cmv100] [PMID: 26743722]

[69]
Hennings, J.M.; Schaaf, L.; Fulda, S. Glucose metabolism and antidepressant medication. Curr. Pharm. Des.,  2012, 18(36), 5900-5919.
 [http://dx.doi.org/10.2174/138161212803523662] [PMID: 22681169]

[70]
Knol, M.J.; Geerlings, M.I.; Egberts, A.C.G.; Gorter, K.J.; Grobbee, D.E.; Heerdink, E.R. No increased incidence of diabetes in antidepressant users. Int. Clin. Psychopharmacol.,  2007, 22(6), 382-386.
 [http://dx.doi.org/10.1097/YIC.0b013e3282202c0e] [PMID: 17917558]

[71]
Erenmemisoglu, A.; Ozdogan, U.K.; Saraymen, R.; Tutus, A. Effect of some antidepressants on glycaemia and insulin levels of normoglycaemic and alloxan-induced hyperglycaemic mice. J. Pharm. Pharmacol.,  2010, 51(6), 741-743.
 [http://dx.doi.org/10.1211/0022357991772899] [PMID: 10454053]

[72]
Yamada, J.; Sugimoto, Y.; Inoue, K. Selective serotonin reuptake inhibitors fluoxetine and fluvoxamine induce hyperglycemia by different mechanisms. Eur. J. Pharmacol.,  1999, 382(3), 211-215.
 [http://dx.doi.org/10.1016/S0014-2999(99)00593-2] [PMID: 10556672]

[73]
Thorré, K.; Chaouloff, F.; Sarre, S.; Meeusen, R.; Ebinger, G.; Michotte, Y. Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats. Brain Res.,  1997, 772(1-2), 209-216.
 [http://dx.doi.org/10.1016/S0006-8993(97)00841-X] [PMID: 9406974]

[74]
Aksu, I.; Ates, M.; Baykara, B.; Kiray, M.; Sisman, A.R.; Buyuk, E.; Baykara, B.; Cetinkaya, C.; Gumus, H.; Uysal, N. Anxiety correlates to decreased blood and prefrontal cortex IGF-1 levels in streptozotocin induced diabetes. Neurosci. Lett.,  2012, 531(2), 176-181.
 [http://dx.doi.org/10.1016/j.neulet.2012.10.045] [PMID: 23123774]

[75]
Gambeta, E.; de Souza, C.P.; de Morais, H.; Zanoveli, J.M. Reestablishment of the hyperglycemia to the normal levels seems not to be essential to the anxiolytic-like effect induced by insulin. Metab. Brain Dis.,  2016, 31(3), 563-571.
 [http://dx.doi.org/10.1007/s11011-015-9770-1] [PMID: 26608284]

[76]
Rebolledo-Solleiro, D.; Araiza, L.F.O.; Broccoli, L.; Hansson, A.C.; Rocha-Arrieta, L.L.; Aguilar-Roblero, R.; Crespo-Ramírez, M.; Fuxe, K.; Pérez de la, M.M. Dopamine D1 receptor activity is involved in the increased anxiety levels observed in STZ-induced diabetes in rats. Behav. Brain Res.,  2016, 313, 293-301.
 [http://dx.doi.org/10.1016/j.bbr.2016.06.060] [PMID: 27374159]

[77]
Aswar, U.; Chepurwar, S.; Shintre, S.; Aswar, M. Telmisartan attenuates diabetes induced depression in rats. Pharmacol. Rep.,  2017, 69(2), 358-364.
 [http://dx.doi.org/10.1016/j.pharep.2016.12.004] [PMID: 28189098]

[78]
Caliskan, H.; Akat, F.; Tatar, Y.; Zaloglu, N.; Dursun, A.D.; Bastug, M.; Ficicilar, H. Effects of exercise training on anxiety in diabetic rats. Behav. Brain Res.,  2019, 376, 112084.
 [http://dx.doi.org/10.1016/j.bbr.2019.112084] [PMID: 31356829]

[79]
Farbood, Y.; Rashno, M.; Ghaderi, S.; Khoshnam, S.E.; Sarkaki, A.; Rashidi, K.; Rashno, M.; Badavi, M. Ellagic acid protects against diabetes-associated behavioral deficits in rats: Possible involved mechanisms. Life Sci.,  2019, 225, 8-19.
 [http://dx.doi.org/10.1016/j.lfs.2019.03.078] [PMID: 30943382]

[80]
de Souza, C.P.; Gambeta, E.; Stern, C.A.J.; Zanoveli, J.M. Posttraumatic stress disorder-type behaviors in streptozotocin-induced diabetic rats can be prevented by prolonged treatment with vitamin E. Behav. Brain Res.,  2019, 359, 749-754.
 [http://dx.doi.org/10.1016/j.bbr.2018.09.008] [PMID: 30219262]

[81]
Bikri, S.; Aboussaleh, Y.; Berrani, A.; Louragli, I.; Hafid, A.; Chakib, S.; Ahami, A. Effects of date seeds administration on anxiety and depressive symptoms in streptozotocin-induced diabetic rats: biochemical and behavioral evidences. J. Basic Clin. Physiol. Pharmacol.,  2021, 32(6), 1031-1040.
 [http://dx.doi.org/10.1515/jbcpp-2020-0225] [PMID: 33705613]

[82]
de Lima Silva, A.H.B.; Radulski, D.R.; Pereira, G.S.; Acco, A.; Zanoveli, J.M. A single injection of pregabalin induces short- and long-term beneficial effects on fear memory and anxiety-like behavior in rats with experimental type-1 diabetes mellitus. Metab. Brain Dis.,  2022, 37(4), 1095-1110.
 [http://dx.doi.org/10.1007/s11011-022-00936-3] [PMID: 35239142]

[83]
Chaves, Y.C.; Genaro, K.; Stern, C.A.; de Oliveira, G.G.; de Souza, C.J.A.; da Cunha, J.M.; Zanoveli, J.M. Two-weeks treatment with cannabidiol improves biophysical and behavioral deficits associated with experimental type-1 diabetes. Neurosci. Lett.,  2020, 729, 135020.
 [http://dx.doi.org/10.1016/j.neulet.2020.135020] [PMID: 32360935]

[84]
Maciel, R.M.; Carvalho, F.B.; Olabiyi, A.A.; Schmatz, R.; Gutierres, J.M.; Stefanello, N.; Zanini, D.; Rosa, M.M.; Andrade, C.M.; Rubin, M.A.; Schetinger, M.R.; Morsch, V.M.; Danesi, C.C.; Lopes, S.T.A. Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities. Biomed. Pharmacother.,  2016, 84, 559-568.
 [http://dx.doi.org/10.1016/j.biopha.2016.09.069] [PMID: 27694000]

[85]
Rajabi, M.; Mohaddes, G.; Farajdokht, F.; Nayebi Rad, S.; Mesgari, M.; Babri, S. Impact of loganin on pro-inflammatory cytokines and depression- and anxiety-like behaviors in male diabetic rats. Physiol. Int.,  2018, 105(2), 116-126.
 [http://dx.doi.org/10.1556/2060.105.2018.2.8] [PMID: 29975123]

[86]
Ghaderi, S.; Rashno, M.; Nesari, A.; Khoshnam, S.E.; Sarkaki, A.; Khorsandi, L.; Farbood, Y.; Rashidi, K. Sesamin alleviates diabetes-associated behavioral deficits in rats: The role of inflammatory and neurotrophic factors. Int. Immunopharmacol.,  2021, 92, 107356.
 [http://dx.doi.org/10.1016/j.intimp.2020.107356] [PMID: 33440305]

[87]
Pereira, M.M.; de Morais, H.; dos Santos Silva, E.; Corso, C.R.; Adami, E.R.; Carlos, R.M.; Acco, A.; Zanoveli, J.M. The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes. Metab. Brain Dis.,  2018, 33(5), 1573-1584.
 [http://dx.doi.org/10.1007/s11011-018-0264-9] [PMID: 29934859]

[88]
Rahmani, G.; Farajdokht, F.; Mohaddes, G.; Babri, S.; Ebrahimi, V.; Ebrahimi, H. Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats. Arch. Physiol. Biochem.,  2020, 126(2), 95-100.
 [http://dx.doi.org/10.1080/13813455.2018.1494746] [PMID: 30169970]

[89]
Rajizadeh, M.A.; Aminizadeh, A.H.; Esmaeilpour, K.; Bejeshk, M.A.; Sadeghi, A.; Salimi, F. Investigating the effects of Citrullus colocynthis on cognitive performance and anxiety-like behaviors in STZ-induced diabetic rats. Int. J. Neurosci.,  2021, 26, 1-13.
 [PMID: 33848216]

[90]
Şahin, T.D.; Göçmez, S.S.; Eraldemir, F.C.; Utkan, T. Anxiolytic-like and antidepressant-like effects of resveratrol in streptozotocin-induced diabetic rats. Noro Psikiyatri Arsivi,  2019, 56(2), 144-149.
 [PMID: 31223249]

[91]
Jiang, W.; Tang, Y.Y.; Zhu, W.W.; Li, C.; Zhang, P.; Li, R.Q.; Chen, Y.J.; Zou, W.; Tang, X.Q. PI3K/AKT pathway mediates the antidepressant- and anxiolytic-like roles of hydrogen sulfide in streptozotocin-induced diabetic rats via promoting hippocampal neurogenesis. Neurotoxicology,  2021, 85, 201-208.
 [http://dx.doi.org/10.1016/j.neuro.2021.05.016] [PMID: 34087334]

[92]
Wang, H.; Shi, X.; Qiu, M.; Lv, S.; Zheng, H.; Niu, B.; Liu, H. Hydrogen Sulfide plays an important role by influencing NLRP3 inflammasome. Int. J. Biol. Sci.,  2020, 16(14), 2752-2760.
 [http://dx.doi.org/10.7150/ijbs.47595] [PMID: 33110394]

[93]
Kotagale, N.; Rahangdale, S.; Borkar, A.; Singh, K.; Ikhar, A.; Takale, N.; Umekar, M.; Taksande, B. Possible involvement of agmatine in neuropharmacological actions of metformin in diabetic mice. Eur. J. Pharmacol.,  2021, 907, 174255.
 [http://dx.doi.org/10.1016/j.ejphar.2021.174255] [PMID: 34129880]

[94]
Yuan, P.; Zhang, J.; Li, L.; Song, Z. Fluoxetine attenuated anxiety-like behaviors in streptozotocin-induced diabetic mice by mitigating the inflammation. Mediators Inflamm.,  2019, 2019, 1-8.
 [http://dx.doi.org/10.1155/2019/4315038] [PMID: 31396018]

[95]
López-Rubalcava, C.; Paez-Martinez, N.; Oikawa, J. Blockade of corticosteroid receptors induces anxiolytic-like effects in streptozotocin-induced diabetic mice, and synergizes with diazepam. Behav. Pharmacol.,  2013, 24(4), 320-327.
 [http://dx.doi.org/10.1097/FBP.0b013e3283637de2] [PMID: 23764904]

[96]
Li, Z.G.; Zhang, W.; Grunberger, G.; Sima, A.A.F. Hippocampal neuronal apoptosis in type 1 diabetes. Brain Res.,  2002, 946(2), 221-231.
 [http://dx.doi.org/10.1016/S0006-8993(02)02887-1] [PMID: 12137925]

[97]
Yamamoto, Y.; Akiyoshi, J.; Kiyota, A.; Katsuragi, S.; Tsutsumi, T.; Isogawa, K.; Nagayama, H. Increased anxiety behavior in OLETF rats without cholecystokinin-A receptor. Brain Res. Bull.,  2000, 53(6), 789-792.
 [http://dx.doi.org/10.1016/S0361-9230(00)00407-X] [PMID: 11179844]

[98]
Ochi, R.; Fujita, N.; Goto, N.; Nguyen, S.T.; Le, D.T.; Matsushita, K.; Ono, T.; Nishijo, H.; Urakawa, S. Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: Implication for anxiety-like behavior. J. Physiol. Sci.,  2020, 70(1), 42.
 [http://dx.doi.org/10.1186/s12576-020-00771-0] [PMID: 32938363]

[99]
Ochi, R.; Fujita, N.; Goto, N.; Takaishi, K.; Oshima, T.; Nguyen, S.T.; Nishijo, H.; Urakawa, S. Medial prefrontal area reductions, altered expressions of cholecystokinin, parvalbumin, and activating transcription factor 4 in the corticolimbic system, and altered emotional behavior in a progressive rat model of type 2 diabetes. PLoS One,  2021, 16(9), e0256655.
 [http://dx.doi.org/10.1371/journal.pone.0256655] [PMID: 34506507]

[100]
Khare, P.; Datusalia, A.K.; Sharma, S.S. Parthenolide, an NF-κB inhibitor ameliorates diabetes-induced behavioural deficit, neurotransmitter imbalance and neuroinflammation in type 2 diabetes rat model. Neuromolecular Med.,  2017, 19(1), 101-112.
 [http://dx.doi.org/10.1007/s12017-016-8434-6] [PMID: 27553015]

[101]
Jabri, M.A.; Rtibi, K.; Sebai, H. Chamomile decoction mitigates high fat diet-induced anxiety-like behavior, neuroinflammation and cerebral ROS overload. Nutr. Neurosci.,  2022, 25(7), 1350-1361.
 [http://dx.doi.org/10.1080/1028415X.2020.1859727] [PMID: 33314994]

[102]
Pechlivanova, D.; Krumova, E.; Kostadinova, N.; Mitreva-Staleva, J.; Grozdanov, P.; Stoynev, A. Protective effects of losartan on some type 2 diabetes mellitus-induced complications in Wistar and spontaneously hypertensive rats. Metab. Brain Dis.,  2020, 35(3), 527-538.
 [http://dx.doi.org/10.1007/s11011-020-00534-1] [PMID: 31997264]

[103]
Garabadu, D.; Krishnamurthy, S. Diazepam potentiates the antidiabetic, antistress and anxiolytic activities of metformin in type-2 diabetes mellitus with cooccurring stress in experimental animals. BioMed Res. Int.,  2014, 2014, 1-15.
 [http://dx.doi.org/10.1155/2014/693074] [PMID: 24995322]

[104]
Morshedi, M.; Valenlia, K.B.; Hosseinifard, E.S.; Shahabi, P.; Abbasi, M.M.; Ghorbani, M.; Barzegari, A.; Sadigh-Eteghad, S.; Saghafi-Asl, M. Beneficial psychological effects of novel psychobiotics in diabetic rats: The interaction among the gut, blood and amygdala. J. Nutr. Biochem.,  2018, 57, 145-152.
 [http://dx.doi.org/10.1016/j.jnutbio.2018.03.022] [PMID: 29730508]

[105]
Hosseinifard, E.S.; Morshedi, M.; Bavafa-Valenlia, K.; Saghafi-Asl, M. The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: Possible link between gut microbiota and brain regions. Eur. J. Nutr.,  2019, 58(8), 3361-3375.
 [http://dx.doi.org/10.1007/s00394-019-01924-7] [PMID: 30826905]

[106]
Matinfar, P.; Peeri, M.; Azarbayjani, M.A. Swimming exercise attenuates anxiety-like behavior by reducing brain oxidative stress in type 2 diabetic mice. Physiol. Behav.,  2021, 237, 113449.
 [http://dx.doi.org/10.1016/j.physbeh.2021.113449] [PMID: 33945802]

[107]
Murotomi, K.; Umeno, A.; Yasunaga, M.; Shichiri, M.; Ishida, N.; Koike, T.; Matsuo, T.; Abe, H.; Yoshida, Y.; Nakajima, Y. Oleuropein-rich diet attenuates hyperglycemia and impaired glucose tolerance in type 2 diabetes model mouse. J. Agric. Food Chem.,  2015, 63(30), 6715-6722.
 [http://dx.doi.org/10.1021/acs.jafc.5b00556] [PMID: 26165358]

[108]
Stranahan, A.M.; Arumugam, T.V.; Cutler, R.G.; Lee, K.; Egan, J.M.; Mattson, M.P. Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat. Neurosci.,  2008, 11(3), 309-317.
 [http://dx.doi.org/10.1038/nn2055] [PMID: 18278039]

[109]
Dorsemans, A.C.; Couret, D.; Hoarau, A.; Meilhac, O.; Lefebvre d’Hellencourt, C.; Diotel, N. Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and zebrafish models. Neurogenesis,  2017, 4(1), e1281862.
 [http://dx.doi.org/10.1080/23262133.2017.1281862] [PMID: 28439518]

[110]
Biessels, G.J.; Kamal, A.; Urban, I.J.A.; Spruijt, B.M.; Erkelens, D.W.; Gispen, W.H. Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: Effects of insulin treatment. Brain Res.,  1998, 800(1), 125-135.
 [http://dx.doi.org/10.1016/S0006-8993(98)00510-1] [PMID: 9685609]

[111]
Popoviç, M.; Biessels, G.J.; Isaacson, R.L.; Gispen, W.H. Learning and memory in streptozotocin-induced diabetic rats in a novel spatial/object discrimination task. Behav. Brain Res.,  2001, 122(2), 201-207.
 [http://dx.doi.org/10.1016/S0166-4328(01)00186-3] [PMID: 11334650]

[112]
Stranahan, A.M. Models and mechanisms for hippocampal dysfunction in obesity and diabetes. Neuroscience,  2015, 309, 125-139.
 [http://dx.doi.org/10.1016/j.neuroscience.2015.04.045] [PMID: 25934036]

[113]
Moreira, P.; Santos, M.; Sena, C.; Nunes, E.; Seiça, R.; Oliveira, C. CoQ10 therapy attenuates amyloid β-peptide toxicity in brain mitochondria isolated from aged diabetic rats. Exp. Neurol.,  2005, 196(1), 112-119.
 [http://dx.doi.org/10.1016/j.expneurol.2005.07.012] [PMID: 16126199]

[114]
Moreira, P.I.; Santos, M.S.; Moreno, A.M.; Seiça, R.; Oliveira, C.R. Increased vulnerability of brain mitochondria in diabetic (Goto-Kakizaki) rats with aging and amyloid-beta exposure. Diabetes,  2003, 52(6), 1449-1456.
 [http://dx.doi.org/10.2337/diabetes.52.6.1449] [PMID: 12765956]

[115]
Kuhad, A.; Bishnoi, M.; Tiwari, V.; Chopra, K. Suppression of NF-κβ signaling pathway by tocotrienol can prevent diabetes associated cognitive deficits. Pharmacol. Biochem. Behav.,  2009, 92(2), 251-259.
 [http://dx.doi.org/10.1016/j.pbb.2008.12.012] [PMID: 19138703]

[116]
Sima, A.A.F.; Zhang, W.; Kreipke, C.W.; Rafols, J.A.; Hoffman, W.H. Inflammation in diabetic encephalopathy is prevented by c-peptide. Rev. Diabet. Stud.,  2009, 6(1), 37-42.
 [http://dx.doi.org/10.1900/RDS.2009.6.37] [PMID: 19557294]

[117]
Nagayach, A.; Patro, N.; Patro, I. Astrocytic and microglial response in experimentally induced diabetic rat brain. Metab. Brain Dis.,  2014, 29(3), 747-761.
 [http://dx.doi.org/10.1007/s11011-014-9562-z] [PMID: 24833555]

[118]
Kuhad, A.; Sethi, R.; Chopra, K. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sci.,  2008, 83(3-4), 128-134.
 [http://dx.doi.org/10.1016/j.lfs.2008.05.013] [PMID: 18585396]

[119]
Stranahan, A.M.; Lee, K.; Pistell, P.J.; Nelson, C.M.; Readal, N.; Miller, M.G.; Spangler, E.L.; Ingram, D.K.; Mattson, M.P. Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels. Neurobiol. Learn. Mem.,  2008, 90(2), 479-483. b
 [http://dx.doi.org/10.1016/j.nlm.2008.05.005] [PMID: 18579418]

[120]
Magariños, A.M.; McEwen, B.S. Experimental diabetes in rats causes hippocampal dendritic and synaptic reorganization and increased glucocorticoid reactivity to stress. Proc. Natl. Acad. Sci.,  2000, 97(20), 11056-11061.
 [http://dx.doi.org/10.1073/pnas.97.20.11056] [PMID: 11005876]

[121]
Grillo, C.A.; Piroli, G.G.; Wood, G.E.; Reznikov, L.R.; McEwen, B.S.; Reagan, L.P. Immunocytochemical analysis of synaptic proteins provides new insights into diabetes-mediated plasticity in the rat hippocampus. Neuroscience,  2005, 136(2), 477-486.
 [http://dx.doi.org/10.1016/j.neuroscience.2005.08.019] [PMID: 16226381]

[122]
Beauquis, J.; Homo-Delarche, F.; Revsin, Y.; De Nicola, A.F.; Saravia, F. Brain alterations in autoimmune and pharmacological models of diabetes mellitus: Focus on hypothalamic-pituitary-adrenocortical axis disturbances. Neuroimmunomodulation,  2008, 15(1), 61-67.
 [http://dx.doi.org/10.1159/000135625] [PMID: 18667801]

[123]
Saravia, F.E.; Revsin, Y.; Gonzalez Deniselle, M.C.; Gonzalez, S.L.; Roig, P.; Lima, A.; Homo-Delarche, F.; De Nicola, A.F. Increased astrocyte reactivity in the hippocampus of murine models of type 1 diabetes: The nonobese diabetic (NOD) and streptozotocin-treated mice. Brain Res.,  2002, 957(2), 345-353.
 [http://dx.doi.org/10.1016/S0006-8993(02)03675-2] [PMID: 12445977]

[124]
Duarte, J.M.N.; Carvalho, R.A.; Cunha, R.A.; Gruetter, R. Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. J. Neurochem.,  2009, 111(2), 368-379.
 [http://dx.doi.org/10.1111/j.1471-4159.2009.06349.x] [PMID: 19694901]

[125]
Gaspar, J.M.; Baptista, F.I.; Galvão, J.; Castilho, Á.F.; Cunha, R.A.; Ambrósio, A.F. Diabetes differentially affects the content of exocytotic proteins in hippocampal and retinal nerve terminals. Neuroscience,  2010, 169(4), 1589-1600.
 [http://dx.doi.org/10.1016/j.neuroscience.2010.06.021] [PMID: 20600668]

[126]
Man, H.Y.; Lin, J.W.; Ju, W.H.; Ahmadian, G.; Liu, L.; Becker, L.E.; Sheng, M.; Wang, Y.T. Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron,  2000, 25(3), 649-662.
 [http://dx.doi.org/10.1016/S0896-6273(00)81067-3] [PMID: 10774732]

[127]
Zhao, W.Q.; Alkon, D.L. Role of insulin and insulin receptor in learning and memory. Mol. Cell. Endocrinol.,  2001, 177(1-2), 125-134.
 [http://dx.doi.org/10.1016/S0303-7207(01)00455-5] [PMID: 11377828]

[128]
Ahmadian, G.; Ju, W.; Liu, L.; Wyszynski, M.; Lee, S.H.; Dunah, A.W.; Taghibiglou, C.; Wang, Y.; Lu, J.; Wong, T.P.; Sheng, M.; Wang, Y.T. Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA receptor endocytosis and LTD. EMBO J.,  2004, 23(5), 1040-1050.
 [http://dx.doi.org/10.1038/sj.emboj.7600126] [PMID: 14976558]

[129]
Francis, G.J.; Martinez, J.A.; Liu, W.Q.; Xu, K.; Ayer, A.; Fine, J.; Tuor, U.I.; Glazner, G.; Hanson, L.R.; Frey, W.H., II; Toth, C. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain,  2008, 131(Pt 12), 3311-3334.
 [PMID: 19015157]

[130]
Lee, C.C.; Huang, C.C.; Hsu, K.S. Insulin promotes dendritic spine and synapse formation by the PI3K/Akt/mTOR and Rac1 signaling pathways. Neuropharmacology,  2011, 61(4), 867-879.
 [http://dx.doi.org/10.1016/j.neuropharm.2011.06.003] [PMID: 21683721]

[131]
Craft, S.; Stennis, W.G. Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurol.,  2004, 3(3), 169-178.
 [http://dx.doi.org/10.1016/S1474-4422(04)00681-7] [PMID: 14980532]

[132]
Freude, S.; Plum, L.; Schnitker, J.; Leeser, U.; Udelhoven, M.; Krone, W.; Bruning, J.C.; Schubert, M. Peripheral hyperinsulinemia promotes tau phosphorylation in vivo. Diabetes,  2005, 54(12), 3343-3348.
 [http://dx.doi.org/10.2337/diabetes.54.12.3343] [PMID: 16306348]

[133]
Iqbal, K.; Liu, F.; Gong, C.X.; Alonso, A.C.; Grundke-Iqbal, I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol.,  2009, 118(1), 53-69.
 [http://dx.doi.org/10.1007/s00401-009-0486-3] [PMID: 19184068]

[134]
Liu, Y.; Liu, F.; Grundke-Iqbal, I.; Iqbal, K.; Gong, C.X. Deficient brain insulin signalling pathway in Alzheimer’s disease and diabetes. J. Pathol.,  2011, 225(1), 54-62.
 [http://dx.doi.org/10.1002/path.2912] [PMID: 21598254]

[135]
Qu, Z.; Jiao, Z.; Sun, X.; Zhao, Y.; Ren, J.; Xu, G. Effects of streptozotocin-induced diabetes on tau phosphorylation in the rat brain. Brain Res.,  2011, 1383, 300-306.
 [http://dx.doi.org/10.1016/j.brainres.2011.01.084] [PMID: 21281610]

[136]
Jackson-Guilford, J.; Leander, J.D.; Nisenbaum, L.K. The effect of streptozotocin-induced diabetes on cell proliferation in the rat dentate gyrus. Neurosci. Lett.,  2000, 293(2), 91-94.
 [http://dx.doi.org/10.1016/S0304-3940(00)01502-0] [PMID: 11027841]

[137]
McEwen, B.S.; Magariños, A.M.; Reagan, L.P. Studies of hormone action in the hippocampal formation. J. Psychosom. Res.,  2002, 53(4), 883-890.
 [http://dx.doi.org/10.1016/S0022-3999(02)00307-0] [PMID: 12377298]

[138]
Li, Z.; Zhang, W.; Sima, A.A.F. The role of impaired insulin/IGF action in primary diabetic encephalopathy. Brain Res.,  2005, 1037(1-2), 12-24.
 [http://dx.doi.org/10.1016/j.brainres.2004.11.063] [PMID: 15777748]

[139]
Sima, A.A.F.; Li, Z. The effect of C-peptide on cognitive dysfunction and hippocampal apoptosis in type 1 diabetic rats. Diabetes,  2005, 54(5), 1497-1505.
 [http://dx.doi.org/10.2337/diabetes.54.5.1497] [PMID: 15855338]

[140]
Beauquis, J.; Roig, P.; Homo-Delarche, F.; De Nicola, A.; Saravia, F. Reduced hippocampal neurogenesis and number of hilar neurones in streptozotocin-induced diabetic mice: Reversion by antidepressant treatment. Eur. J. Neurosci.,  2006, 23(6), 1539-1546.
 [http://dx.doi.org/10.1111/j.1460-9568.2006.04691.x] [PMID: 16553617]

[141]
Malone, J.I.; Hanna, S.; Saporta, S.; Mervis, R.F.; Park, C.R.; Chong, L.; Diamond, D.M. Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memory. Pediatr. Diabetes,  2008, 9(6), 531-539.
 [http://dx.doi.org/10.1111/j.1399-5448.2008.00431.x] [PMID: 19067891]

[142]
Zhang, L.; Bruce-Keller, A.J.; Dasuri, K.; Nguyen, A.; Liu, Y.; Keller, J.N. Diet-induced metabolic disturbances as modulators of brain homeostasis. Biochim. Biophys. Acta Mol. Basis Dis.,  2009, 1792(5), 417-422.
 [http://dx.doi.org/10.1016/j.bbadis.2008.09.006] [PMID: 18926905]

[143]
Hernández-Fonseca, J.P.; Rincón, J.; Pedreañez, A.; Viera, N.; Arcaya, J.L.; Carrizo, E.; Mosquera, J. Structural and ultrastructural analysis of cerebral cortex, cerebellum, and hypothalamus from diabetic rats. Exp. Diabetes Res.,  2009, 2009, 1-12.
 [http://dx.doi.org/10.1155/2009/329632] [PMID: 19812703]

[144]
Alvarez-Nölting, R.; Arnal, E.; Barcia, J.M.; Miranda, M.; Romero, F.J. Protection by DHA of early hippocampal changes in diabetes: Possible role of CREB and NF-κB. Neurochem. Res.,  2012, 37(1), 105-115.
 [http://dx.doi.org/10.1007/s11064-011-0588-x] [PMID: 21909958]

[145]
Guyot, L.L.; Diaz, F.G.; O’Regan, M.H.; Song, D.; Phillis, J.W. The effect of streptozotocin-induced diabetes on the release of excitotoxic and other amino acids from the ischemic rat cerebral cortex. Neurosurgery,  2001, 48(2), 385-390.
 [PMID: 11220383]

[146]
Duarte, J.M.N.; Oses, J.P.; Rodrigues, R.J.; Cunha, R.A. Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats. Neuroscience,  2007, 149(2), 382-391.
 [http://dx.doi.org/10.1016/j.neuroscience.2007.08.005] [PMID: 17869435]

[147]
Satoh, E.; Takahashi, A. Experimental diabetes enhances Ca2+ mobilization and glutamate exocytosis in cerebral synaptosomes from mice. Diabetes Res. Clin. Pract.,  2008, 81(2), e14-e17.
 [http://dx.doi.org/10.1016/j.diabres.2008.04.017] [PMID: 18508149]

[148]
Sherin, A.; Anu, J.; Peeyush, K.T.; Smijin, S.; Anitha, M.; Roshni, B.T.; Paulose, C.S. Cholinergic and GABAergic receptor functional deficit in the hippocampus of insulin-induced hypoglycemic and streptozotocin-induced diabetic rats. Neuroscience,  2012, 202, 69-76.
 [http://dx.doi.org/10.1016/j.neuroscience.2011.11.058] [PMID: 22155651]

[149]
Gardoni, F.; Kamal, A.; Bellone, C.; Biessels, G.J.; Ramakers, G.M.J.; Cattabeni, F.; Gispen, W.H.; Di Luca, M. Effects of streptozotocin-diabetes on the hippocampal NMDA receptor complex in rats. J. Neurochem.,  2002, 80(3), 438-447.
 [http://dx.doi.org/10.1046/j.0022-3042.2001.00713.x] [PMID: 11908465]

[150]
Biessels, G.J.; van der Heide, L.P.; Kamal, A.; Bleys, R.L.A.W.; Gispen, W.H. Ageing and diabetes: Implications for brain function. Eur. J. Pharmacol.,  2002, 441(1-2), 1-14.
 [http://dx.doi.org/10.1016/S0014-2999(02)01486-3] [PMID: 12007915]

[151]
Heng, L.J.; Yang, R.H.; Jia, D. Diabetes impairs learning performance through affecting membrane excitability of hippocampal pyramidal neurons. Behav. Brain Res.,  2011, 224(2), 250-258.
 [http://dx.doi.org/10.1016/j.bbr.2011.05.043] [PMID: 21722676]

[152]
Greenwood, C.E.; Winocur, G. Cognitive impairment in rats fed high-fat diets: A specific effect of saturated fatty-acid intake. Behav. Neurosci.,  1996, 110(3), 451-459.
 [http://dx.doi.org/10.1037/0735-7044.110.3.451] [PMID: 8888990]

[153]
Winocur, G.; Greenwood, C.E.; Piroli, G.G.; Grillo, C.A.; Reznikov, L.R.; Reagan, L.P.; McEwen, B.S. Memory impairment in obese Zucker rats: An investigation of cognitive function in an animal model of insulin resistance and obesity. Behav. Neurosci.,  2005, 119(5), 1389-1395.
 [http://dx.doi.org/10.1037/0735-7044.119.5.1389] [PMID: 16300445]

[154]
Pratchayasakul, W.; Kerdphoo, S.; Petsophonsakul, P.; Pongchaidecha, A.; Chattipakorn, N.; Chattipakorn, S.C. Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone. Life Sci.,  2011, 88(13-14), 619-627.
 [http://dx.doi.org/10.1016/j.lfs.2011.02.003] [PMID: 21315737]

[155]
Miao, Y.; He, T.; Zhu, Y.; Li, W.; Wang, B.; Zhong, Y. Activation of hippocampal CREB by rolipram partially recovers balance between TNF-α and IL-10 levels and improves cognitive deficits in diabetic rats. Cell. Mol. Neurobiol.,  2015, 35(8), 1157-1164.
 [http://dx.doi.org/10.1007/s10571-015-0209-3] [PMID: 26001770]

[156]
Pipatpiboon, N.; Pratchayasakul, W.; Chattipakorn, N.; Chattipakorn, S.C. PPARγ agonist improves neuronal insulin receptor function in hippocampus and brain mitochondria function in rats with insulin resistance induced by long term high-fat diets. Endocrinology,  2012, 153(1), 329-338.
 [http://dx.doi.org/10.1210/en.2011-1502] [PMID: 22109891]

[157]
Kim, B.; Backus, C.; Oh, S.; Hayes, J.M.; Feldman, E.L. Increased tau phosphorylation and cleavage in mouse models of type 1 and type 2 diabetes. Endocrinology,  2009, 150(12), 5294-5301.
 [http://dx.doi.org/10.1210/en.2009-0695] [PMID: 19819959]

[158]
Qiu, W.; Folstein, M. Insulin, insulin-degrading enzyme and amyloid-β peptide in Alzheimer’s disease: Review and hypothesis. Neurobiol. Aging,  2006, 27(2), 190-198.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2005.01.004] [PMID: 16399206]

[159]
Oomura, Y.; Hori, N.; Shiraishi, T.; Fukunaga, K.; Takeda, H.; Tsuji, M.; Matsumiya, T.; Ishibashi, M.; Aou, S.; Li, X.L.; Kohno, D.; Uramura, K.; Sougawa, H.; Yada, T.; Wayner, M.J.; Sasaki, K. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats. Peptides,  2006, 27(11), 2738-2749.
 [http://dx.doi.org/10.1016/j.peptides.2006.07.001] [PMID: 16914228]

[160]
Moult, P.R.; Harvey, J. Hormonal regulation of hippocampal dendritic morphology and synaptic plasticity. Cell Adhes. Migr.,  2008, 2(4), 269-275.
 [http://dx.doi.org/10.4161/cam.2.4.6354] [PMID: 19262152]

[161]
Marwarha, G.; Ghribi, O. Leptin signaling and Alzheimer’s disease. Am. J. Neurodegener. Dis.,  2012, 1(3), 245-265.
 [PMID: 23383396]

[162]
Moon, H.S.; Dalamaga, M.; Kim, S.Y.; Polyzos, S.A.; Hamnvik, O.P.; Magkos, F.; Paruthi, J.; Mantzoros, C.S. Leptin’s role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr. Rev.,  2013, 34(3), 377-412.
 [http://dx.doi.org/10.1210/er.2012-1053] [PMID: 23475416]

[163]
Balland, E.; Cowley, M.A. New insights in leptin resistance mechanisms in mice. Front. Neuroendocrinol.,  2015, 39, 59-65.
 [http://dx.doi.org/10.1016/j.yfrne.2015.09.004] [PMID: 26410445]

[164]
Alzoubi, K.H. M, A.; Aleisa, A.; Alkadhi, K.A. Impairment of long-term potentiation in the CA1, but not dentate gyrus, of the hippocampus in Obese Zucker rats: Role of calcineurin and phosphorylated CaMKII. J. Mol. Neurosci.,  2005, 27(3), 337-347.
 [http://dx.doi.org/10.1385/JMN:27:3:337] [PMID: 16280604]

[165]
Tomassoni, D.; Nwankwo, I.E.; Gabrielli, M.G.; Bhatt, S.; Muhammad, A.B.; Lokhandwala, M.F.; Tayebati, S.K.; Amenta, F. Astrogliosis in the brain of obese Zucker rat: A model of metabolic syndrome. Neurosci. Lett.,  2013, 543, 136-141.
 [http://dx.doi.org/10.1016/j.neulet.2013.03.025] [PMID: 23545209]

[166]
Beauquis, J.; Roig, P.; De Nicola, A.F.; Saravia, F. Neuronal plasticity and antidepressants in the diabetic brain. Ann. N. Y. Acad. Sci.,  2009, 1153(1), 203-208.
 [http://dx.doi.org/10.1111/j.1749-6632.2008.03983.x] [PMID: 19236343]

[167]
Rivera, P.; Pérez-Martín, M.; Pavón, F.J.; Serrano, A.; Crespillo, A.; Cifuentes, M.; López-Ávalos, M.D.; Grondona, J.M.; Vida, M.; Fernández-Llebrez, P.; de Fonseca, F.R.; Suárez, J. Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus. PLoS One,  2013, 8(5), e64750.
 [http://dx.doi.org/10.1371/journal.pone.0064750] [PMID: 23741384]

[168]
Pancani, T.; Anderson, K.L.; Brewer, L.D.; Kadish, I.; DeMoll, C.; Landfield, P.W.; Blalock, E.M.; Porter, N.M.; Thibault, O. Effect of high-fat diet on metabolic indices, cognition, and neuronal physiology in aging F344 rats. Neurobiol. Aging,  2013, 34(8), 1977-1987.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2013.02.019] [PMID: 23545425]
Cite As
Current Neuropharmacology

Affective and Cognitive Impairments in Rodent Models of Diabetes

Abstract

Graphical Abstract
