Age-Related Changes of Cholinergic Markers in the Rat Brain

Yufu, Fumie; Egashira, Toru; Yamanaka, Yasumitsu

doi:10.1254/jjp.66.247

Cited by 28 publications

(14 citation statements)

References 48 publications

(51 reference statements)

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“…Because it is well-known that the functioning cholinergic system can be damaged by cerebral ischemia (14), we compared various cholinergic biochemical markers (mAChR and ChAT activity) in the cortex, hippocampus and striatum of the brains of aged (24 month) and young (6 weeks) rats treated with permanent 2VO. We previously reported that the investigation of brain cholinergic systems in aged control rats could provide useful information pertaining to age and age-related disorders in humans (9,10). However, in this study, ChAT activity and the number of mAChR in aged 2VO rats decreased nearly 10-20% as compared with those in aged control rats.…”

Section: Choline Acetyltransferase Activity Assaycontrasting

confidence: 58%

“…We these data should aid in establishing a model of senile also investigated the effect of long-term administration dementia that could be used to investigate potentially of bifemelane on cholinergic markers in aged 2VO rats; therapeutic drugs (9,10). This model, however, employbifemelane is known to be an effective treatment for ed rats that were simply aged, not true models of senile cerebrovascular disease in clinical trials as well as in dementia.…”

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confidence: 99%

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Effects of Bifemelane on Muscarinic Receptors and Choline Acetyltransferase in the Brains of Aged Rats Following Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Carotid Arteries

Egashira

Takayama

Yamanaka

1996

Japanese Journal of Pharmacology

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ABSTRACT-Cerebralhypoperfusion was chronically induced in aged rats via permanent bilateral occlusion of common carotid arteries (2VO). Marked reduction of the Bmax value of the muscarinic receptors (mAChR) in both the cortex and striatum and the Vma,, value of choline acetyltransferase (ChAT) activity in the cortex, hippocampus and striatum were observed as compared with those of control aged rats. No significant changes in mAChR and ChAT activity were observed between young control rats and young 2VO rats. One month post-surgery in aged rats, daily doses of bifemelane (10 mg/kg) or aniracetam (50 mg/kg) were administered orally over a 4-week period. Administration of bifemelane significantly increased Bmax values and decreased apparent Kd values for 3H-quinuclidinyl benzilate (QNB) in mAChR in the striatum. Chronic administration of bifemelane or aniracetam also enhanced ChAT activity in the cortex, hippocampus and striatum. In particular, administration of bifemelane resulted in a significant increase in Vma., values of ChAT in all three brain regions, while no significant change in Km values for ChAT was observed. These results suggest that bifemelane is responsible for this activity, thereby enhancing the functioning system of CNS cholinergic neurons of cerebral hypoperfused aged rats.Keywords: Aged rat, Permanent bilateral occlusion of common carotid arteries, Muscarinic receptor, Choline acetyltransferase, Bifemelane, Aniracetam A number of drugs and substances have been devedecreased in patients with senile dementia, such as in the loped as means to decrease the symptoms of memory imcase of Alzheimer's disease (11, 12). Senile dementia is pairment observed in patients with senile dementia, and characterized by marked cognitive impairments that their effects have been studied in animal models (1-5).parallel the progression of neuronal damage (13). PermaThe results of these experiments, however, have not yet nent bilateral occlusion of common carotid arteries (2VO) yielded sufficient data to be useful in the clinical setting. in rats is used as a model for brain ischemia (14). In adVarious kinds of animal models have been developed to dition, it is known that permanent 2VO induces chronic study human dementia; these include drug-(2), brain cerebral hypoperfusion (15). lesion-(6-8), or transient ischemia-(3) induced amnesiaIn the present study, we examined whether chronic in rodents.cerebral hypoperfusion induced by permanent 2VO in We previously reported that the investigation of brain aged rats would result in neuronal damage and observed cholinergic systems in aged rats could provide informathe subsequent muscarinic receptor (mAChR) concentration concerning age-related disorders in humans and that tion and choline acetyltransferase (ChAT) activity. We these data should aid in establishing a model of senile also investigated the effect of long-term administration dementia that could be used to investigate potentially of bifemelane on cholinergic markers in aged 2VO rats; therapeutic drugs (9, 10). This mo...

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Section: Choline Acetyltransferase Activity Assaycontrasting

confidence: 58%

mentioning

confidence: 99%

Effects of Bifemelane on Muscarinic Receptors and Choline Acetyltransferase in the Brains of Aged Rats Following Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Carotid Arteries

Egashira

Takayama

Yamanaka

1996

Japanese Journal of Pharmacology

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“…The basal forebrain cholinergic (BFC) system is particularly vulnerable during aging (Yufu et al 1994;Smith and Booze 1995). One structure adversely affected by the loss of BFC system integrity is the hippocampus (De Lacalle et al 1994).…”

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confidence: 99%

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

Weible¹,

Oh²,

Lee³

et al. 2004

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Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive deficits associated with normal aging and aging-related dementias. Trace eyeblink conditioning (EBC), a hippocampusand forebrain-dependent learning paradigm, is impaired in both aged rabbits and aged humans, attributable in part to cholinergic dysfunction. In the present study, we examined the effects of galantamine (3 mg/kg), a cholinesterase inhibitor and nAChR allosteric potentiating ligand, on the acquisition of trace EBC in aged (30-33 months) and young (2-3 months) female rabbits. Trace EBC involves the association of a conditioned stimulus (CS) with an unconditioned stimulus (US), separated by a stimulus-free trace interval. Repeated CS-US pairings results in the development of the conditioned eyeblink response (CR) prior to US onset. Aged rabbits receiving daily injections of galantamine (Aged/Gal) exhibited significant improvements compared with age-matched controls in trials to eight CRs in 10 trial block criterion (P = 0.0402) as well as performance across 20 d of training [F(1,21) = 5.114, P = 0.0345]. Mean onset and peak latency of CRs exhibited by Aged/Gal rabbits also differed significantly [F (1,21) = 6.120/6.582, P = 0.0220/0.0180, respectively] compared with age-matched controls, resembling more closely CR timing of young drug and control rabbits. Galantamine did not improve acquisition rates in young rabbits compared with age-matched controls. These data indicate that by enhancing nicotinic and muscarinic transmission, galantamine is effective in offsetting the learning deficits associated with decreased cholinergic transmission in the aging brain.

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“…An age-related decline in AChE activity was reported in all brain regions (Michalek et al 1989;Bisso et al 1991). Decreased AChE activity observed in the cerebral cortex of 90 weeks old control group suggests a loss of postsynaptic enzyme activity during ageing (Sirvio et al 1988;Yufu et al 1994). Hyperglycaemia caused significant increase in AChE activity of both 7 and 90 weeks old rat groups, whereas insulin administration reversed this effect.…”

Section: Discussionmentioning

confidence: 88%

“…In our present study on muscarinic M1 receptor binding using [ 3 H]QNB with pirenzepine, we found that M1 receptor number decreased significantly in the cerebral cortex of control old rats compared to the young rats with a significant increase in the affinity. Total specific binding sites for the muscarinic antagonist, L-QNB showed a decline with age (Briggs et al 1982) and age-related increase in the affinity of mAChRs was observed in the cortical regions of rats (Yufu et al 1994). Studies using selective M1 antagonist, [ 3 H]-pirenzepine ([ 3 H]PZ) showed decreased receptor density in the cortex of aged rats compared to young rats (Schwarz et al 1990;Ehlert and Tran 1990).…”

Section: Discussionmentioning

confidence: 99%

Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets

et al. 2009

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We investigated acetylcholine esterase (AChE) activity, acetylcholine and muscarinic M1, M3 receptors kinetics in the cerebral cortex of young and old streptozotocin induced and insulin treated diabetic rats. The role of muscarinic receptors in intracellular calcium release from pancreatic islets was studied in vitro. Wistar rats of 7 and 90-weeks old were used. All studies were done in cerebral cortex. AChE assay was done by spectrophotometric method. Radioreceptor binding assays were done for Acetylcholine, Muscarinic M1 and M3 receptors using specific ligands. Calcium imaging was done using fluo4-AM in pancreatic cells. Ninety-weeks old control rats showed significantly decreased Vmax and increased Km for AChE compared to 7-weeks old control rats. An increased Vmax observed in both 7 and 90-weeks old diabetic groups with significant decrease in Km. Scatchard analysis using specific agonists showed significant decrease in the B (max) and K (d) of acetylcholine and muscarinic M1 receptors in 90-weeks old control rats compared to 7-weeks old control. Binding studies for M3 receptors showed no significant change compared to 7-weeks old control. Acetylcholine, muscarinic M1 and M3 receptor number significantly increased in 90-weeks old diabetic rat groups compared to their respective controls. Insulin treatment significantly reversed the binding parameters to near control compared to diabetic group. In vitro studies showed that acetylcholine through muscarinic M1 and M3 receptors' stimulated calcium release from the pancreatic islets. Thus our studies suggest that Insulin signaling play an important part in differentially regulating pancreatic cholinergic activity, and the diabetes mediated cortical dysfunctions with age.

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Age-Related Changes of Cholinergic Markers in the Rat Brain

Cited by 28 publications

References 48 publications

Effects of Bifemelane on Muscarinic Receptors and Choline Acetyltransferase in the Brains of Aged Rats Following Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Carotid Arteries

Effects of Bifemelane on Muscarinic Receptors and Choline Acetyltransferase in the Brains of Aged Rats Following Chronic Cerebral Hypoperfusion Induced by Permanent Occlusion of Bilateral Carotid Arteries

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

Acetylcholine and muscarinic receptor function in cerebral cortex of diabetic young and old male Wistar rats and the role of muscarinic receptors in calcium release from pancreatic islets

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