Objective To study the protective effects of clioquinol on the hippocampal neuronal apoptosis and learning and memory functions of epileptic mice. Methods The epileptic mice model were built by pilocarpine in this study. Mice were divided into 3 groups: a control group (saline), an epilepsy group (pilocarpine and saline) and a clioquinol group (pilocarpine and clioquinol). Then the distribution of zinc in hippocampus was observed by autometallography. The morphological changes and the number of neurons were checked by Nissl staining. The expression of Bcl-2 and Bax protein were detected by immunoblotting. Enzyme linked immunosorbent assay was used to check the expression of caspases-9 and caspases-3 protein. The seizure times, seizure level and seizure duration were checked by behavioral observation. The learning and memory ability was shown by T maze and Y maze. Results In the clioquinol group, the distribution of zinc in hippocampus reduced significantly, the damage of hippocampal neurons was improved and the number of neurons increased, the expression of Bcl-2 protein increased, while the expression of Bax, caspases-9 and caspases-3 protein decreased. The ratio of Bcl-2 to Bax increased. The seizure times, seizure level and seizure duration decreased. The ability of learning and memory was improved (P<0.01). Conclusions Clioquinol can protect hippocampal neurons and improve the learning and memory functions of epileptic mice.
Dou Xiaona, Li Xia, Li Xinyu, Zhang Li
. Protective effects of clioquinol on the hippocampal neuronal apoptosis and learning and memory functions of epileptic mice[J]. Chinese Journal of Clinical Anatomy, 2022
, 40(1)
: 33
-38
.
DOI: 10.13418/j.issn.1001-165x.2022.1.07
[1] Yu W, Bei T, Yi W, et al. Cholinergic signaling, neural excitability, and epilepsy[J]. Molecules. 2021, 26(8): 2258. DOI: 10.3390/molecules 26082258.
[2] Shibley H, Smith BN. Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice[J]. Epilepsy Res, 2002, 49(2): 109-120. DOI: 10.1016/s0920-1211(02)00012-8.
[3] Racine RJ, Steingart M, Mcintyre DC. Development of kindling-prone and kindling resistant rats: selective breeding and electrophysiological studies[J]. Epilepsy Res, 1999, 35(3): 183-195. DOI: 10.1016/s0920-1211(99)00013-3.
[4] Doboszewska U, Młyniec K, Wlaz A, et al. Zinc signaling and epilepsy[J]. Pharmacol Ther, 2019, 193: 156-177. DOI: 10.1016/j.pharmthera. 2018.08.013.
[5] Singh S. Zinc oxide nanoparticles impacts: cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity[J]. Toxicol Mech Methods, 2019, 29(4): 300-311. DOI: 10.1080/15376516.2018.1553221.
[6] Jin MF, Ni H, L LL. Leptin maintained zinc homeostasis against glutamate- induced excitotoxicity by preventing mitophagy-mediated mitochondrial activation in HT22 hippocampal neuronal cells[J]. Front Neurol, 2018, 9: 322. DOI: 10.3389/fneur.2018.00322.
[7] Jeong HJ, Song HL, Kho AR , et al. The transient receptor potential melastatin 7 (TRPM7) inhibitors suppress seizure-induced neuron death by inhibiting zinc neurotoxicity[J]. Int J Mol Sci, 2020, 21(21): 7897. DOI: 10.3390/ijms21217897.
[8] Carver CM, Chuang SH, Reddy DS. Zinc selectively blocks neurosteroid- sensitive extrasynaptic δGABAA receptors in the hippocampus[J]. J Neurosci, 2016, 36(31): 8070-8077. DOI: 10.1523/JNEUROSCI.3393-15.2016.
[9]Alpdogan S, Neumaier F, Hescheler J, et al. Experimentally induced convulsive seizures are modulated in part by zinc ions through the pharmacoresistant Cav2.3 calcium channel[J]. Cell Physiol Biochem, 2020, 54(2): 180-194. DOI: 10.33594/000000213.
[10]Wang DD, Jin MF, Li LL, et al. PRG5 knockout precipitates late-onset hypersusceptibility to pilocarpine-induced juvenile seizures by exacerbating hippocampal zinc signaling-mediated mitochondrial damage[J]. Front Neurosci, 2021, 15: 715555. DOI: 10.3389/fnins. 2021. 715555.
[11]Ni H, Jiang YW, Tao LY, et al. ZnT-1, ZnT-3, CaMK II, PRG-1 expressions in hippocampus following neonatal seizure-induced cognitive deficit in rats[J]. Toxicol Lett, 2009, 184(3): 145-150. DOI: 10.1016/j.toxlet.2008.11.003.
[12]Udayabanu M, Kumaran D, Katyal A. Free chelatable zinc modulates the cholinergic function during hypobaric hypoxia-induced neuronal damage: an in vivo study[J]. Neuroscience, 2012, 202: 434-445. DOI: 10.1016/j.neuroscience.2011.11.022.
[13]牟苇杭, 杨慧云, 刘迢迢, 等. 高协同纳米递药系统经鼻给药对淀粉样前体蛋白与早老素1转基因小鼠认知功能的影响[J]. 中华老年心脑血管病杂志, 2020, 22(9): 974-978. DOI: 10.3969/j.issn.1009-0126. 2020. 09.020.
[14]李晓瑜, 翟晓杰, 陈骏萍. 氯碘羟喹对术后认知功能的影响[J]. 现代实用医学, 2020, 32(9): 1107-1109. DOI: 10.3969/j.issn.1671-0800. 2020. 09.041.
[15]李霞, 刘明晨, 贾雨山, 等. 干扰锌代谢对癫痫小鼠易感性、学习记忆和海马神经元损伤的影响研究[J]. 中国临床解剖学杂志, 2019, 37(1): 45-50. DOI: 10.13418/j.issn.1001-165x.2019.01.010.
