Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia

Tanaka, Ken; Ogawa, Norio; Mizukawa, Kiminao; Asanuma, Masato; Kondo, Yoichi; Nishibayashi, Sakiko; Mori, Akitane

doi:10.1007/bf00966804

Cited by 38 publications

(21 citation statements)

References 21 publications

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“…The exact mechanisms by which CTS and THA normalize the expression levels of m 3 -and m 5 -receptor subtype genes are unclear. However, in vivo studies have demonstrated that the stimulation of muscarinic ACh receptors provides neuroprotection against transient ischemia-induced neuronal cell death, even when reperfusion has been carried out in an animal model of transient forebrain ischemia (37,38). Moreover, stimulation of the m 3 -receptor subtype reportedly triggers protection of ischemia-induced myocardial injuries (39) and apoptotic cerebellar granule neurons (40) in a manner reversible by m 3 -receptor antagonists.…”

Section: Discussionmentioning

confidence: 99%

Chotosan, a Kampo Formula, Ameliorates Chronic Cerebral Hypoperfusion-Induced Deficits in Object Recognition Behaviors and Central Cholinergic Systems in Mice

et al. 2007

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Abstract. We previously demonstrated that the Kampo formula chotosan (CTS) ameliorated spatial cognitive impairment via central cholinergic systems in a chronic cerebral hypoperfusion (P2VO) mouse model. In this study, the object discrimination tasks were used to determine if the ameliorative effects of CTS on P2VO-induced cognitive deficits are a characteristic pharmacological profile of this formula, with the aim of clarifying the mechanisms by which CTS enhances central cholinergic function in P2VO mice. The cholinesterase inhibitor tacrine (THA) and Kampo formula saikokeishito (SKT) were used as controls. P2VO impaired object discrimination performance in the object recognition, location, and context tests. Daily administration of CTS (750 mg / kg, p.o.) and THA (2.5 mg / kg, i.p.) improved the object discrimination deficits, whereas SKT (750 mg / kg, p.o.) did not. In ex vivo assays, tacrine but not CTS or SKT inhibited cortical cholinesterase activity. P2VO reduced the mRNA expression of m 3 and m 5 muscarinic receptors and choline acetyltransferase but not that of other muscarinic receptor subtypes in the cerebral cortex. Daily administration of CTS and THA but not SKT reversed these expression changes. These results suggest that CTS and THA improve P2VO-induced cognitive impairment by normalizing the deficit of central cholinergic systems and that the beneficial effect on P2VO-induced cognitive deficits is a distinctive pharmacological characteristic of CTS.

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Section: Discussionmentioning

confidence: 99%

Chotosan, a Kampo Formula, Ameliorates Chronic Cerebral Hypoperfusion-Induced Deficits in Object Recognition Behaviors and Central Cholinergic Systems in Mice

et al. 2007

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“…Post-ischemic administration of rivastigmine showed the same result in prevention of the decrease in cholinergic activity in head trauma rats [110] together with reduced motor and neurological deficits and faster recovery. Moreover, the investigators also demonstrated that prevention of delayed neuron death and amelioration of accumulation of astrocytes in the hippocampal CA1 region contributed to the protective mechanisms of rivastigmine [108,111] . These protective effects could be prevented by the simultaneous injection of mecamylamine, but not by scopolamine [110] , suggesting that the therapeutic effects on cerebrovascular type dementia of rivastigmine may be related to nAChR-mediated cholinergic www.nature.com/aps Wang J et al Acta Pharmacologica Sinica npg enhancement.…”

Section: Rivastigminementioning

confidence: 95%

“…Pretreatment with rivastigmine mitigated the abnormalities in the cerebral cholinergic system in the BCCAO-induced gerbil ischemic model [108,109] . Post-ischemic administration of rivastigmine showed the same result in prevention of the decrease in cholinergic activity in head trauma rats [110] together with reduced motor and neurological deficits and faster recovery.…”

Section: Rivastigminementioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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“…It has been suggested that rivastigmine may be effective in treating subcortical ischemic vascular dementia (228)(229)(230)(231). Thus, in patients with two APOE 4 alleles, ChE-Is may treat both the cholinergic deficit associated with AD pathology and the subcortical ischemic pathology that may be more likely in these patients.…”

Section: In Modulating Response To Che-ismentioning

confidence: 99%

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

Lane

Farlow

2005

Journal of Lipid Research

157

128

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Acetylcholinesterase inhibitor ENA-713 protects against ischemia-induced decrease in pre- and postsynaptic cholinergic indices in the gerbil brain following transient ischemia

Cited by 38 publications

References 21 publications

Chotosan, a Kampo Formula, Ameliorates Chronic Cerebral Hypoperfusion-Induced Deficits in Object Recognition Behaviors and Central Cholinergic Systems in Mice

Chotosan, a Kampo Formula, Ameliorates Chronic Cerebral Hypoperfusion-Induced Deficits in Object Recognition Behaviors and Central Cholinergic Systems in Mice

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease

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