Protective effect of donepezil hydrochloride on cerebral ischemia/reperfusion injury in mice

Wang,Tianjun; Lv,Peiyuan; Jin,Wei; Zhang,Hezhen; Lang,Jingfang; Fan,Mingyue

doi:10.3892/mmr.2013.1823

Protective effect of donepezil hydrochloride on cerebral ischemia/reperfusion injury in mice

Authors:
- Tianjun Wang
- Peiyuan Lv
- Wei Jin
- Hezhen Zhang
- Jingfang Lang
- Mingyue Fan
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Affiliations: Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
Published online on: November 22, 2013 https://doi.org/10.3892/mmr.2013.1823
Pages: 509-514

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Abstract

The aim of this study was to investigate the effects of donepezil hydrochloride (DH) on the expression of the calpain I-cyclin-dependent kinase5/p25 (CDK5/p25) pathway in the hippocampal CA1 region in mice with cerebral ischemia-reperfusion (I/R). Mice were randomly divided and assigned to the sham operation group (SO), the model group (MG) and the DH treatment group (TG). The pathological appearance of the hippocampal CA1 region and the expression of calpain I and CDK5/p25, were observed on the 4th, 6th and 8th week of the I/R surgery. Within the same time periods, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were also determined. At each postoperative time point, the normal neuron count in the hippocampal CA1 region in the MG was significantly lower than that in the SO (P<0.05), whereas the calpain I and CDK5/p25 expression, SOD activity and MDA content in the MG were significantly higher than those in the SO (P<0.05). The normal neuron count of the hippocampal CA1 region in the TG increased significantly (P<0.05), whereas the calpain I and CDK5/p25 expression, SOD activity and MDA content in the TG were significantly lower than those in the MG (P<0.05). DH has protective effects against ischemic damage. The ability of DH to improve learning and memory in mice may be due to its ability to decrease the expression of the calpain I-CDK5/p25 pathway and reduce oxidative damage.

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1	Yan BC, Park JH, Ahn JH, Lee JC, Won MH and Kang IJ: Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury. J Neurol Sci. 330:111–116. 2013. View Article : Google Scholar
2	Tu Q, Wang R, Ding B, Zhong W and Cao H: Protective and antioxidant effect of Danshen polysaccharides on cerebral ischemia/reperfusion injury in rats. Int J Biol Macromol. 60:268–271. 2013. View Article : Google Scholar : PubMed/NCBI
3	Wang Q, Kalogeris TJ, Wang M, Jones AW and Korthuis RJ: Antecedent ethanol attenuates cerebral ischemia/reperfusion-induced leukocyte-endothelial adhesive interactions and delayed neuronal death: role of large conductance, Ca²⁺-activated K⁺ channels. Microcirculation. 17:427–438. 2010.
4	Zhang F, Guo A, Liu C, Comb M and Hu B: Phosphorylation and assembly of glutamate receptors after brain ischemia. Stroke. 44:170–176. 2013. View Article : Google Scholar : PubMed/NCBI
5	Racay P, Tatarkova Z, Chomova M, Hatok J, Kaplan P and Dobrota D: Mitochondrial calcium transport and mitochondrial dysfunction after global brain ischemia in rat hippocampus. Neurochem Res. 34:1469–1478. 2009. View Article : Google Scholar : PubMed/NCBI
6	Peng S, Kuang Z, Zhang Y, Xu H and Cheng Q: The protective effects and potential mechanism of Calpain inhibitor Calpeptin against focal cerebral ischemia-reperfusion injury in rats. Mol Biol Rep. 38:905–912. 2011. View Article : Google Scholar : PubMed/NCBI
7	Su SC and Tsai LH: Cyclin-dependent kinases in brain development and disease. Annu Rev Cell Dev Biol. 27:465–491. 2011. View Article : Google Scholar : PubMed/NCBI
8	Chen J and Wang ZF: Roles of cyclin-dependent kinase 5 in central nervous system development and neurodegenerative diseases. Sheng Li Xue Bao. 62:295–308. 2010.PubMed/NCBI
9	Ghosh A, Sarkar S, Mandal AK and Das N: Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS One. 8:e577352013. View Article : Google Scholar : PubMed/NCBI
10	Harry GJ and Lefebvre d’Hellencourt C: Dentate gyrus: alterations that occur with hippocampal injury. Neurotoxicology. 24:343–356. 2003. View Article : Google Scholar : PubMed/NCBI
11	Knapp LT and Klann E: Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory? J Neurosci Res. 70:1–7. 2002. View Article : Google Scholar : PubMed/NCBI
12	Kishida KT and Klann E: Sources and targets of reactive oxygen species in synaptic plasticity and memory. Antioxid Redox Signal. 9:233–244. 2007. View Article : Google Scholar : PubMed/NCBI
13	Zhou L, Aon MA, Liu T and O’Rourke B: Dynamic modulation of Ca²⁺ sparks by mitochondrial oscillations in isolated guinea pig cardiomyocytes under oxidative stress. J Mol Cell Cardiol. 51:632–639. 2011.
14	Winblad B, Engedal K, Soininen H, et al: A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 57:489–495. 2001.PubMed/NCBI
15	Fujiki M, Kobayashi H, Uchida S, Inoue R and Ishii K: Neuroprotective effect of donepezil, a nicotinic acetylcholine-receptor activator, on cerebral infarction in rats. Brain Res. 1043:236–241. 2005. View Article : Google Scholar : PubMed/NCBI
16	Takada Y, Yonezawa A, Kume T, et al: Nicotinic acetylcholine receptor-mediated neuroprotection by donepezil against glutamate neurotoxicity in rat cortical neurons. J Pharmacol Exp Ther. 306:772–777. 2003. View Article : Google Scholar
17	Akasofu S, Kimura M, Kosasa T, Sawada K and Ogura H: Study of neuroprotection of donepezil, a therapy for Alzheimer’s disease. Chem Biol Interact. 175:222–226. 2008.
18	Akasofu S, Sawada K, Kosasa T, Hihara H, Ogura H and Akaike A: Donepezil attenuates excitotoxic damage induced by membrane depolarization of cortical neurons exposed to veratridine. Eur J Pharmacol. 588:189–197. 2008. View Article : Google Scholar : PubMed/NCBI
19	Fang S, Yan B, Wang D, et al: Chronic effects of venlafaxine on synaptophysin and neuronal cell adhesion molecule in the hippocampus of cerebral ischemic mice. Biochem Cell Biol. 88:655–663. 2010.PubMed/NCBI
20	Min D, Mao X, Wu K, et al: Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils. Neurosci Lett. 510:29–33. 2012. View Article : Google Scholar : PubMed/NCBI
21	Block F: Global ischemia and behavioural deficits. Prog Neurobiol. 58:279–295. 1999. View Article : Google Scholar : PubMed/NCBI
22	von Euler M, Bendel O, Bueters T, Sandin J and von Euler G: Profound but transient deficits in learning and memory after global ischemia using a novel water maze test. Behav Brain Res. 166:204–210. 2006.PubMed/NCBI
23	Shukla V, Skuntz S and Pant HC: Deregulated Cdk5 activity is involved in inducing Alzheimer’s disease. Arch Med Res. 43:655–662. 2012.PubMed/NCBI
24	Mitsios N, Pennucci R, Krupinski J, et al: Expression of cyclin-dependent kinase 5 mRNA and protein in the human brain following acute ischemic stroke. Brain Pathol. 17:11–23. 2007. View Article : Google Scholar : PubMed/NCBI
25	Christophe M and Nicolas S: Mitochondria: a target for neuroprotective interventions in cerebral ischemia-reperfusion. Curr Pharm Des. 12:739–757. 2006. View Article : Google Scholar : PubMed/NCBI
26	Guo C, Tong L, Xi M, Yang H, Dong H and Wen A: Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury in rats. J Ethnopharmacol. 144:768–774. 2012. View Article : Google Scholar : PubMed/NCBI
27	Liu C, Wu JL, Gu J, et al: Baicalein improves cognitive deficits induced by chronic cerebral hypoperfusion in rats. Pharmacol Biochem Behav. 86:423–430. 2007. View Article : Google Scholar : PubMed/NCBI
28	Rhee SG, Yang KS, Kang SW, Woo HA and Chang TS: Controlled elimination of intracellular H(2)O(2): Regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification. Antioxid Redox Signal. 7:619–626. 2005. View Article : Google Scholar : PubMed/NCBI
29	Rashidian J, Rousseaux MW, Venderova K, et al: Essential role of cytoplasmic cdk5 and Prx2 in multiple ischemic injury models, in vivo. J Neurosci. 29:12497–12505. 2009. View Article : Google Scholar : PubMed/NCBI
30	Bendel O, Prunell G, Stenqvist A, et al: Experimental subarachnoid hemorrhage induces changes in the levels of hippocampal NMDA receptor subunit mRNA. Brain Res Mol Brain Res. 137:119–125. 2005. View Article : Google Scholar : PubMed/NCBI
31	Koh PO: Ischemic injury decreases parvalbumin expression in a middle cerebral artery occlusion animal model and glutamate-exposed HT22 cells. Neurosci Lett. 512:17–21. 2012. View Article : Google Scholar
32	Kliper E, Bashat DB, Bornstein NM, et al: Cognitive decline after stroke: relation to inflammatory biomarkers and hippocampal volume. Stroke. 44:1433–1435. 2013.PubMed/NCBI