Protective effect of donepezil in a primary culture of rat cortical neurons exposed to oxygen–glucose deprivation

Akasofu, Shigeru; Kosasa, Takashi; Kimura, M.; Kubota, Atsuhito

doi:10.1016/s0014-2999(03)01865-x

Cited by 68 publications

(48 citation statements)

References 23 publications

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“…Donepezil pretreatment also markedly inhibited OGD-induced decrease in the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). 39) Pretreatment with donepezil at concentrations higher than 0.1 mM significantly and dose-dependently inhibited OGD-induced cell in-jury measured by lactate dehydrogenase release in primary culture of the rat cerebral cortex 40) ; however, significant protection against OGD-induced neuronal damage was not observed with galantamine, tacrine or rivastigmine pretreatment. 41) These data showed that pretreatment with donepezil has protective effects against artificial ischemia in PC12 cells and primary culture of rat cortical neurons and, at least in the OGD model of ischemia, donepezil has the most potent protective effect against neuronal damage.…”

Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

“…The potency of donepezil has been confirmed with in vivo studies on spatial cognitive impairment in a rat hypoperfusion model of ischemia using the escape latency model. 42) These studies suggest, from several points of view, that the neuroprotective effects of acetylcholinesterase inhibitors are not due to AChE inhibition: (1) Donepezil but not other acetylcholinesterase inhibitors could not protect neurons from OGD-induced injury, 40) (2) physostigmine, the strongest AChE inhibitor among those tested, did not protect neurons in our study, (3) the neuroprotective action of donepezil, galantamine and tacrine was observed in a concentration-dependent manner at concentrations much higher than their half-maximal inhibitory concentration (Fig. 1), (4) acetylcholinesterase inhibitors have no effect when administered at the same time as glutamate.…”

Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

“…39,40) Pretreatment with donepezil (1 mM) for 2 h before OGD inhibited OGD-induced cell injury in PC12 cells measured by cell morphology. Donepezil pretreatment also markedly inhibited OGD-induced decrease in the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT).…”

Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

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Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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Protection of neurons from neuronal damage and cell death in neurodegenerative disease is a major challenge in neuroscience research. Donepezil, galantamine and tacrine are acetylcholinesterase inhibitors used for the treatment of Alzheimer's disease, and were believed to be symptomatic drugs whose therapeutic effects are achieved by slowing the hydrolysis of acetylcholine at synaptic termini. However, recent accumulated evidence strongly suggests that these acetylcholinesterase inhibitors also possess neuroprotective properties whose mechanism is independent of acetylcholinesterase inhibition. We have shown that acetylcholinesterase inhibitors protect neurons from glutamate-induced neurotoxicity in the primary culture of rat cortical neurons. It was also found that acetylcholinesterase inhibitor treatment induces up-regulation of nicotinic receptor expression levels, a property which may also have some bearing on their therapeutic effects. We next showed that a a4 and a a7-nicotinic receptors play important roles in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation. Our results also demonstrate the important roles of the phosphatidylinositol 3-kinase pathway downstream of nicotinic receptors in protecting neurons from death and up-regulating nicotinic receptors. This review summarizes recent findings on the roles of the nicotinic receptor in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation.

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Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

Section: Neuroprotective Properties Of Acetyl-cholinesterase Inhibitorsmentioning

confidence: 99%

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Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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“…2,11,12) Muscarinic receptors appear to be implicated in inhibition of delayed neuronal death after transient ischemia 13,14) probably via increasing neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). 15) Moreover, stimulation of nicotinic a7 receptors reportedly shows a similar protective effect on ischemia-induced neuronal injury.…”

mentioning

confidence: 99%

Preventive Effect of Chotosan, a Kampo Medicine, on Transient Ischemia-Induced Learning Deficit Is Mediated by Stimulation of Muscarinic M1 But Not Nicotinic Receptor

Zhao

Murakami

Tohda

et al. 2005

Biological & Pharmaceutical Bulletin

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We have previously shown using a water maze task that transient 2 vessel occlusion (T2VO) induced learning deficit in mice and that the deficit was prevented by pre-treatment of mice with chotosan, a Kampo prescription. In this study, we investigated the mechanism underlying the preventive effect of chotosan on T2VO-induced learning deficit. Chotosan administration 1 h before T2VO operation prevented learning impairment. The extract of Uncaria, a major constituent of chotosan, also had a protective effect on learning impairment in T2VO mice, whereas Uncaria-free chotosan had no beneficial effect on maze performance of T2VO mice. The ameliorative effect of chotosan was blocked by pirenzepine, a muscarinic M 1 antagonist, but not by mecamylamine, a nicotinic receptor antagonist. Acetylcholine (ACh) content in the hippocampus of T2VO mice was significantly lower than that in the hippocampus of sham-operated control mice. Chotosan and Uncaria administration attenuated T2VO-induced reduction of ACh levels in the brain. These results suggest that the preventive effect of chotosan on transient ischemia-induced learning impairment is mainly attributable to the effect of Uncaria and that the ameliorative effect is mediated by stimulation of muscarinic M 1 receptor.

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“…Numerous studies have demonstrated that donepezil serves a protective role in cortical neurons by acting on nicotinic acetylcholine receptors (AChR) or the toadstool cholinergic receptor pathway (9,10). In addition, research has suggested that donepezil exerts a protective effect on retinal ganglion cells (RGCs) in vitro and in vivo (11). However, Miki et al (12) reported that a nicotinic AChR (nAChR) inhibitor and a toadstool cholinergic receptor inhibitor did not offset the neuroprotective effect of donepezil.…”

Section: Introductionmentioning

confidence: 99%

Donepezil delays photoreceptor apoptosis induced by N-methyl-N-nitrosourea in mice

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Retinitis pigmentosa (RP) is a group of inherited retinal degeneration diseases characterized by photoreceptor cell death that causes visual disturbances and eventual blindness. Intraperitoneal injection of N-methyl-N-nitrosourea (MNU) causes photoreceptor loss, and is used to create an animal model for investigating the mechanisms that cause retinal degeneration diseases. Donepezil is an acetylcholinesterase inhibitor that has a protective effect on retinal ganglion cells in vitro and in vivo, and it is understood that donepezil increases the expression of a heat shock protein 70 (Hsp70), which serves to protect neurons. Hsp70 functions as a chaperone molecule that protects cells from protein aggregation and assists in the refolding of denatured proteins. In the present study, the effects of donepezil on photoreceptor survival in mice was investigated. It was observed that donepezil upregulates the expression of Hsp70, to increase resistance to MNU-induced photoreceptor cell apoptosis by using its anti-apoptotic properties. In addition, the present study observed that Hsp70 promotes photoreceptor cell survival by upregulating the expression levels of B-cell lymphoma 2 (Bcl-2). In conclusion, the results of the present study indicate that donepezil has the potential to be used as a treatment for retinal degenerative diseases.

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Protective effect of donepezil in a primary culture of rat cortical neurons exposed to oxygen–glucose deprivation

Cited by 68 publications

References 23 publications

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Preventive Effect of Chotosan, a Kampo Medicine, on Transient Ischemia-Induced Learning Deficit Is Mediated by Stimulation of Muscarinic M1 But Not Nicotinic Receptor

Donepezil delays photoreceptor apoptosis induced by N-methyl-N-nitrosourea in mice

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