The Radioprotective Effect of LBP on Neurogenesis and Cognition after Acute Radiation Exposure

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Abstract

Background: Radiation exposure has been linked to the development of brain damage and cognitive impairment, but the protective effect and mechanism of Lycium barbarum pills (LBP) on radiation-induced neurological damage remains to be clarified.

Methods: Behavioral tests and immunohistochemical studies were conducted to evaluate the protective effects of LBP extract (10 g/kg orally daily for 4 weeks) against radiation-induced damage on neurogenesis and cognitive function in Balb/c mice exposed to 5.5 Gy X-ray acute radiation.

Results: The results showed that the LBP extract significantly improved body weight loss, locomotor activity and spatial learning and memory. Immunohistochemical tests revealed that the LBP extract prevented the loss of proliferating cells, newly generated neurons and interneurons, especially in the subgranular area of the dentate gyrus.

Conclusion: The findings suggest that LBP is a potential neuroprotective drug for mitigating radiation-induced neuropsychological disorders.

Graphical Abstract

[1]
Wang, JZ.; Agnihotri, S.; Zadeh, G. Radiation-induced meningiomas. Adv. Exp. Med. Biol., 2023, 1416, 159-173.
[2]
Balmori, A. Evidence for a health risk by RF on humans living around mobile phone base stations: From radiofrequency sickness to cancer. Environ. Res., 2022, 214(Pt 2), 113851.
[3]
Hinrikus, H.; Koppel, T.; Lass, J.; Roosipuu, P.; Bachmann, M. Limiting exposure to radiofrequency radiation: The principles and possible criteria for health protection. Int. J. Radiat. Biol., 2023, 99(8), 1167-1177.
[http://dx.doi.org/10.1080/09553002.2023.2159567] [PMID: 36525560]
[4]
Betlazar, C.; Middleton, R.J.; Banati, R.B.; Liu, G.J. The impact of high and low dose ionising radiation on the central nervous system. Redox Biol., 2016, 9, 144-156.
[http://dx.doi.org/10.1016/j.redox.2016.08.002] [PMID: 27544883]
[5]
Tao, X.G.; Curriero, F.C.; Mahesh, M. Low-dose radiation risks of lymphohematopoietic cancer mortality in U.S. shipyard workers. Radiat. Res., 2022.
[http://dx.doi.org/10.1667/RADE-22-00092.1] [PMID: 36520982]
[6]
Oyefeso, FA. Effects of acute low-moderate dose ionizing radiation to human brain organoids. PLoS One, 2023, 18(5), e0282958.
[7]
Tang, F.R.; Loganovsky, K. Low dose or low dose rate ionizing radiation-induced health effect in the human. J. Environ. Radioact., 2018, 192, 32-47.
[http://dx.doi.org/10.1016/j.jenvrad.2018.05.018] [PMID: 29883875]
[8]
Alton, LA. Exposure to ultraviolet-B radiation increases the susceptibility of mosquitoes to infection with dengue virus. Glob. Chang. Biol., 2023, 29(19), 5540-5551.
[9]
Khan, R.; Basir, M.S.; Akhi, S.Z.; Anik, A.H.; Hossain, S.; Islam, H.M.T.; Islam, A.R.M.T.; Idris, A.M.; Khan, M.H.R.; Aldawood, S.; Tareq, S.M. Radiation exposure and health concerns associated with the environmental geochemistry of relatively higher radioactivity in a fresh water basin. Mar. Pollut. Bull., 2023, 196, 115588.
[http://dx.doi.org/10.1016/j.marpolbul.2023.115588] [PMID: 37806014]
[10]
Kempf, S.J.; Azimzadeh, O.; Atkinson, M.J.; Tapio, S. Long-term effects of ionising radiation on the brain: Cause for concern? Radiat. Environ. Biophys., 2013, 52(1), 5-16.
[http://dx.doi.org/10.1007/s00411-012-0436-7] [PMID: 23100112]
[11]
Cheng, J. A phase 2 study of thalidomide for the treatment of radiation-induced blood-brain barrier injury. Sci. Transl. Med., 2023, 15(684), eabm6543.
[12]
Rübe, C.E. Radiation-induced brain injury: Age dependency of neurocognitive dysfunction following radiotherapy. Cancers, 2023, 15(11), 2999.s.
[13]
Chang, Y.Q. Treatment of radiation-induced brain injury with bisdemethoxycurcumin. Neural. Regen. Res., 2023, 18(2), 416-421.
[14]
Son, Y.; Lee, C.G.; Kim, J.S.; Lee, H.J. Low-dose-rate ionizing radiation affects innate immunity protein IFITM3 in a mouse model of Alzheimer’s disease. Int. J. Radiat. Biol., 2023, 99(11), 1649-1659.
[http://dx.doi.org/10.1080/09553002.2023.2211142] [PMID: 37162420]
[15]
Rivera-Marrero, S. [18F]Amylovis as a potential PET probe for β-amyloid plaque: Synthesis, in silico, in vitro and in vivo evaluations. Curr. Radiopharm., 2019, 12(1), 58-71.
[16]
Zhang, Z. Pregabalin mitigates microglial activation and neuronal injury by inhibiting HMGB1 signaling pathway in radiationinduced brain injury. J. Neuroinflammation., 2022, 19(1), 231.
[17]
Wang, Q. Radioprotective effect of flavonoids on ionizing radiation-induced brain damage. Molecules, 2020, 25(23), 5719.
[http://dx.doi.org/10.3390/molecules25235719]
[18]
Rao, X. Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury. Respir. Res., 2023, 24(1), 25.
[19]
Babu, B. Nanotechnology enabled radioprotectants to reduce space radiation-induced reactive oxidative species. Wiley Interdis-cip. Rev. Nanomed. Nanobiotechnol., 2023, 15(5), e1896.
[20]
Alongi, P. PET evaluation of late cerebral effect in advanced radiation therapy techniques for cranial base tumors. Curr. Radiopharm., 2018, 11(2), 86-91.
[21]
Wang, Q.Q. Ionizing radiation-induced brain cell aging and the potential underlying molecular mechanisms. Cells, 2021, 10(12), 3570.
[22]
Zou, Z.; Chang, H.; Li, H.; Wang, S. Induction of reactive oxygen species: An emerging approach for cancer therapy. Apoptosis, 2017, 22(11), 1321-1335.
[http://dx.doi.org/10.1007/s10495-017-1424-9] [PMID: 28936716]
[23]
Tulard, A.; Hoffschir, F.; de Boisferon, F.H.; Luccioni, C.; Bravard, A. Persistent oxidative stress after ionizing radiation is involved in inherited radiosensitivity. Free Radic. Biol. Med., 2003, 35(1), 68-77.
[http://dx.doi.org/10.1016/S0891-5849(03)00243-0] [PMID: 12826257]
[24]
Kim, W.; Youn, H.; Kang, C.; Youn, B. Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells. Apoptosis, 2015, 20(9), 1242-1252.
[http://dx.doi.org/10.1007/s10495-015-1141-1] [PMID: 26033480]
[25]
Zhu, S. Lycium Barbarum polysaccharide protects HaCaT cells from PM2.5-induced apoptosis via inhibiting oxidative stress, ER stress and autophagy. Redox. Rep., 2022, 27(1), 32-44.
[26]
Meng, J.; Lv, Z.; Guo, M.; Sun, C.; Li, X.; Jiang, Z.; Zhang, W.; Chen, C. A Lycium barbarum extract inhibits β-amyloid toxicity by activating the antioxidant system and mtUPR in a Caenorhabditis elegans model of Alzheimer’s disease. FASEB J., 2022, 36(2), e22156.
[http://dx.doi.org/10.1096/fj.202101116RR] [PMID: 35044707]
[27]
Guo, L. Neuroprotective effects of lycium barbarum berry on neurobehavioral changes and neuronal loss in the hippocam-pus of mice exposed to acute ionizing radiation. Dose Response, 2021, 19(4), 15593258211057768.
[28]
Zhang, J.; Wang, Y.Z.; Yang, W.Z.; Yang, M.Q.; Zhang, J.Y. [Research progress in chemical constituents in plants of Polygonatum and their pharmacological effects] Zhongguo Zhongyao Zazhi, 2019, 44(10), 1989-2008.
[PMID: 31355552]
[29]
Cui, X.; Wang, S.; Cao, H.; Guo, H.; Li, Y.; Xu, F.; Zheng, M.; Xi, X.; Han, C. A review: The bioactivities and pharmacological applications of polygonatum sibiricum polysaccharides. Molecules, 2018, 23(5), 1170.
[http://dx.doi.org/10.3390/molecules23051170] [PMID: 29757991]
[30]
Wang, S.W.; Ren, B.X.; Qian, F.; Luo, X.Z.; Tang, X.; Peng, X.C.; Huang, J.R.; Tang, F.R. Radioprotective effect of epimedium on neurogenesis and cognition after acute radiation exposure. Neurosci. Res., 2019, 145, 46-53.
[http://dx.doi.org/10.1016/j.neures.2018.08.011] [PMID: 30145270]
[31]
Fan, M.; Liu, Y.; Shang, Y.; Xue, Y.; Liang, J.; Huang, Z. JADE2 is essential for hippocampal synaptic plasticity and cognitive functions in mice. Biol. Psychiatry, 2022, 92(10), 800-814.
[http://dx.doi.org/10.1016/j.biopsych.2022.05.021] [PMID: 36008159]
[32]
Takahashi, N.; Misumi, M.; Niwa, Y.; Murakami, H.; Ohishi, W.; Inaba, T.; Nagamachi, A.; Tanaka, S.; Braga Tanaka, I.; Suzuki, G. Effects of radiation on blood pressure and body weight in the spontaneously hypertensive rat model. Are radiation effects on blood pressure affected by genetic background? Radiat. Res., 2020, 193(6), 552-559.
[http://dx.doi.org/10.1667/RR15536.1] [PMID: 32150496]
[33]
Güler-Yüksel, M. Changes in body weight and body composition in patients with active rheumatoid arthritis aged 65+ treated with 2-year low-dose add-on prednisolone in the randomised double-blind placebo-controlled GLORIA trial. RMD Open, 2023, 9(2), e002905.
[34]
Kuijer, E.J.; Steenbergen, L. The microbiota-gut-brain axis in hippocampus-dependent learning and memory: current state and future challenges. Neurosci. Biobehav. Rev., 2023, 152, 105296.
[http://dx.doi.org/10.1016/j.neubiorev.2023.105296] [PMID: 37380040]
[35]
Li, J. Functional specialization and interaction in the amygdala-hippocampus circuit during working memory processing. Nat. Commun., 2023, 14(1), 2921.
[http://dx.doi.org/10.1038/s41467-023-38571-w]
[36]
Krenz, V. Time-dependent memory transformation in hippocampus and neocortex is semantic in nature. Nat. Commun., 2023, 14(1), 6037.
[http://dx.doi.org/10.1038/s41467-023-41648-1]
[37]
Yang, X.; Ma, L.; Ye, Z.; Shi, W.; Zhang, L.; Wang, J.; Yang, H. Radiation-induced bystander effects may contribute to radiation-induced cognitive impairment. Int. J. Radiat. Biol., 2021, 97(3), 329-340.
[http://dx.doi.org/10.1080/09553002.2021.1864498] [PMID: 33332177]
[38]
Yang, B.; Figueroa, D.M.; Hou, Y.; Babbar, M.; Baringer, S.L.; Croteau, D.L.; Bohr, V.A. NEIL1 stimulates neurogenesis and suppresses neuroinflammation after stress. Free Radic. Biol. Med., 2019, 141, 47-58.
[http://dx.doi.org/10.1016/j.freeradbiomed.2019.05.037] [PMID: 31175982]
[39]
Zhao, J.; Zeng, X.; Liu, J.; Liu, X.; Liu, Z.; Wang, B.; Chen, Z.; Dong, Y.; Guo, S.; Cui, M.; Xiao, H.; Liu, X. Marasmius androsaceus mitigates depression-exacerbated intestinal radiation injuries through reprogramming hippocampal miRNA expression. Biomed. Pharmacother., 2023, 165, 115157.
[http://dx.doi.org/10.1016/j.biopha.2023.115157] [PMID: 37454593]
[40]
Wang, H. Early life irradiation-induced hypoplasia and impairment of neurogenesis in the dentate gyrus and adult depression are mediated by microRNA- 34a-5p/T-Cell intracytoplasmic antigen-1 pathway. Cells, 2021, 10(9), 2476.
[41]
Chen, W.; Cheng, X.; Chen, J.; Yi, X.; Nie, D.; Sun, X.; Qin, J.; Tian, M.; Jin, G.; Zhang, X. Lycium barbarum polysaccharides prevent memory and neurogenesis impairments in scopolamine-treated rats. PLoS One, 2014, 9(2), e88076.
[http://dx.doi.org/10.1371/journal.pone.0088076] [PMID: 24505383]
[42]
Yiming, G. ROS-related disruptions to cochlear hair cell and stria vascularis consequently leading to radiation-induced sensori-neural hearing loss. Antioxid Redox Signal, 2023, 0161.
[http://dx.doi.org/10.1089/ars.2022.0161]
[43]
Wang, L.; Liu, C.; Lu, W.; Xu, L.; Kuang, L.; Hua, D. ROS-sensitive Crocin-loaded chitosan microspheres for lung targeting and attenuation of radiation-induced lung injury. Carbohydr. Polym., 2023, 307, 120628.
[http://dx.doi.org/10.1016/j.carbpol.2023.120628] [PMID: 36781279]
[44]
Lee, Y.P. Combination treatment of cordycepin and radiation induces MA-10 mouse Leydig tumor cell death via ROS accumulation and DNA damage. Am. J. Cancer Res., 2023, 13(4), 1329-1346.
[45]
Sundar, V. Psychostimulants influence oxidative stress and redox signatures: the role of DNA methylation. Redox. Rep., 2022, 27(1), 53-59.
[http://dx.doi.org/10.1080/13510002.2022.2043224]
[46]
Ionescu-Tucker, A.; Cotman, C.W. Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiol. Aging, 2021, 107, 86-95.
[http://dx.doi.org/10.1016/j.neurobiolaging.2021.07.014] [PMID: 34416493]
[47]
Singh, A. Oxidative stress: A Key modulator in neurodegenerative diseases. Molecules, 2019, 24(8), 1583.
[48]
Li, X.M.; Ma, Y.L.; Liu, X.J. Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice. J. Ethnopharmacol., 2007, 111(3), 504-511.
[http://dx.doi.org/10.1016/j.jep.2006.12.024] [PMID: 17224253]
[49]
Lam, CS. Neuroprotective mechanism of Lycium barbarum polysaccharides against hippocampal-dependent spatial memory deficits in a rat model of obstructive sleep apnea. PLoS One, 2015, 10(2), e0117990.
[50]
Wang, H. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci. Nutr., 2020, 8(12), 6528-6538.
[51]
Xing, X.; Liu, F.; Xiao, J.; So, K.F. Neuro-protective Mechanisms of Lycium barbarum. Neuromolecular Med., 2016, 18(3), 253-263.
[http://dx.doi.org/10.1007/s12017-016-8393-y] [PMID: 27033360]
[52]
Yao, R. Taohuajing reduces oxidative stress and inflammation in diabetic cardiomyopathy through the sirtuin 1/nucleotide-binding oligomerization domain-like receptor protein 3 pathway. BMC Complement. Med. Ther., 2021, 21(1), 78.
[53]
Mu, J.K.; Zi, L.; Li, Y.Q.; Yu, L.P.; Cui, Z.G.; Shi, T.T.; Zhang, F.; Gu, W.; Hao, J.J.; Yu, J.; Yang, X.X. Jiuzhuan Huangjing Pills relieve mitochondrial dysfunction and attenuate high-fat diet-induced metabolic dysfunction-associated fatty liver disease. Biomed. Pharmacother., 2021, 142, 112092.
[http://dx.doi.org/10.1016/j.biopha.2021.112092] [PMID: 34449316]
[54]
Shen, F.; Song, Z.; Xie, P.; Li, L.; Wang, B.; Peng, D.; Zhu, G. Polygonatum sibiricum polysaccharide prevents depression-like behaviors by reducing oxidative stress, inflammation, and cellular and synaptic damage. J. Ethnopharmacol., 2021, 275, 114164.
[http://dx.doi.org/10.1016/j.jep.2021.114164] [PMID: 33932516]
[55]
Stouffer, M.A.; Khalaf-Nazzal, R.; Cifuentes-Diaz, C.; Albertini, G.; Bandet, E.; Grannec, G.; Lavilla, V.; Deleuze, J.F.; Olaso, R.; Nosten-Bertrand, M.; Francis, F. Doublecortin mutation leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells. Neurobiol. Dis., 2022, 168, 105702.
[http://dx.doi.org/10.1016/j.nbd.2022.105702] [PMID: 35339680]
[56]
Murphy, K.E.; Zhang, E.Y.; Wyatt, E.V.; Sperringer, J.E.; Duncan, B.W.; Maness, P.F. Doublecortin-like kinase 1 facilitates dendritic spine growth of pyramidal neurons in mouse prefrontal cortex. Neuroscience, 2023, 508, 98-109.
[http://dx.doi.org/10.1016/j.neuroscience.2022.08.020] [PMID: 36064052]
[57]
Li, Y.N. Doublecortin-expressing neurons in human cerebral cortex layer II and amygdala from infancy to 100 years old. Mol. Neurobiol., 2023, 60(6), 3464-3485.
[58]
Whoolery, C.W.; Walker, A.K.; Richardson, D.R.; Lucero, M.J.; Reynolds, R.P.; Beddow, D.H.; Clark, K.L.; Shih, H.Y.; LeBlanc, J.A.; Cole, M.G.; Amaral, W.Z.; Mukherjee, S.; Zhang, S.; Ahn, F.; Bulin, S.E.; DeCarolis, N.A.; Rivera, P.D.; Chen, B.P.C.; Yun, S.; Eisch, A.J. Whole-body exposure to 28si-radiation dose-dependently disrupts dentate gyrus neurogenesis and proliferation in the short term and new neuron survival and contextual fear conditioning in the long term. Radiat. Res., 2017, 188(5), 612-631.
[http://dx.doi.org/10.1667/RR14797.1] [PMID: 28945526]
[59]
Ma, Z.Y. Silence of MiR-9 protects depression mice through Notch signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(11), 4961-4970.
[60]
Burke, MW. Dose-related reduction in hippocampal neuronal populations in fetal alcohol exposed vervet monkeys. Brain Sci., 2022, 12(9), 117.
[61]
Medrihan, L.; Umschweif, G.; Sinha, A.; Reed, S.; Lee, J.; Gindinova, K.; Sinha, S.C.; Greengard, P.; Sagi, Y. Reduced Kv3.1 activity in dentate gyrus parvalbumin cells induces vulnerability to depression. Biol. Psychiatry, 2020, 88(5), 405-414.
[http://dx.doi.org/10.1016/j.biopsych.2020.02.1179] [PMID: 32331822]
[62]
Roque, PS. Parvalbumin interneuron loss mediates repeated anesthesia-induced memory deficits in mice. J. Clin. In-vest., 2023, 133(2), 159344.
[63]
Terstege, D.J.; Epp, J.R. Parvalbumin as a sex-specific target in Alzheimer’s disease research – A mini-review. Neurosci. Biobehav. Rev., 2023, 153, 105370.
[http://dx.doi.org/10.1016/j.neubiorev.2023.105370] [PMID: 37619647]
[64]
Shu, S. Prefrontal parvalbumin interneurons deficits mediate early emotional dysfunction in Alzheimer’s dis-ease. Neuropsychopharmacology, 2023, 48(2), 391-401.
[65]
Ji, S.; Ding, X.; Ji, J.; Wu, H.; Sun, R.; Li, X.; Zhang, L.; Tian, Y. Cranial irradiation inhibits hippocampal neurogenesis via DNMT1 and DNMT3A. Oncol. Lett., 2018, 15(3), 2899-2904.
[PMID: 29435016]
[66]
Keijser, J.; Sprekeler, H. Cortical interneurons: Fit for function and fit to function? Evidence from development and evolution. Front. Neural Circuits, 2023, 17, 1172464.
[http://dx.doi.org/10.3389/fncir.2023.1172464] [PMID: 37215503]
[67]
Varghese, N. KCNQ2/3 gain-of-function variants and cell excitability: Differential effects in CA1 versus L2/3 pyramidal neurons. J. Neurosci., 2023, 43(38), 6479-6494.
[68]
Moore, TL. Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function. Geroscience, 2023, 45(3), 1317-1342.
[69]
Dagne, B.A.; Sunay, M.K.; Cayla, N.S.; Ouyang, Y.B.; Knox, S.J.; Giffard, R.G.; Adler, J.R.; Maciver, B. High dose gamma radiation selectively reduces GABAA-slow inhibition. Cureus, 2017, 9(3), e1076.
[http://dx.doi.org/10.7759/cureus.1076] [PMID: 28401026]
[70]
Kokhan, V.S.; Anokhin, P.K.; Belov, O.V.; Gulyaev, M.V. Cortical glutamate/GABA imbalance after combined radiation exposure: relevance to human deep-space missions. Neuroscience, 2019, 416, 295-308.
[http://dx.doi.org/10.1016/j.neuroscience.2019.08.009] [PMID: 31401184]
[71]
Eom, HS. Ionizing radiation induces altered neuronal differentiation by mGluR1 through PI3K-STAT3 signaling in C17.2 mouse neural stem-like cells. PLoS One, 2016, 11(2), e0147538.
[72]
Palma, A. Different mechanisms underlie the metabolic response of GBM stem-like cells to ionizing radiation: Biological and mrs studies on effects of photons and carbon ions. Int. J. Mol. Sci., 2020, 21(14), 5167.
[73]
Mueller, FS. Deficient DNA base-excision repair in the forebrain leads to a sex-specific anxiety-like phenotype in mice. BMC Biol., 2022, 20(1), 170.
[74]
Ábrahám, H.; Kojima, H.; Götzer, K.; Molnár, A.; Tornóczky, T.; Seress, L. Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation. Front. Neuroanat., 2023, 17, 1058370.
[http://dx.doi.org/10.3389/fnana.2023.1058370] [PMID: 36816519]