Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats

Ogawa, Norio; Nomura, Masahiko; Haba, K.; Asanuma, Masato; Tanaka, Kenichi; Hori, Koji; Mori, Akitane

doi:10.1016/0006-8993(92)91631-n

Cited by 16 publications

(2 citation statements)

References 22 publications

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“…These findings agree with our present results from male, 24-month-old Sprague-Dawley rats. Haba et al (32) and Ogawa et al (12) showed that the mAChR level was markedly reduced in all brain regions of aged Fischer rats, but found no change in Kd. Other reports show a decrease in muscarinic receptor binding sites in the cortex, but no change in the hippocampus of Sprague-Dawley (13), Fischer 344 (33,34) or Wistar (35) aged rats.…”

Section: Discussionmentioning

confidence: 96%

“…However, there are conflicting reports from both human and animal studies. Many studies have shown that the lev els of ChAT and mAChR are unchanged (10) or slightly increased with age (11), but decreased levels have also been found (12). These discrepancies could be due in part to the differences in strain or species (13,14), sex (15), tis sue sampling (16,17), assay procedures (18) or the choice of time points during the life cycle used for comparison (19,20).…”

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Age-Related Changes of Cholinergic Markers in the Rat Brain

Yufu

Egashira

Yamanaka

1994

Japanese Journal of Pharmacology

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ABSTRACT-To evaluate whether any degenerative changes affect the brain cholinergic systems during natural aging, we compared various cholinergic biochemical markers (number of muscarinic receptors, mAChR; choline acetyltransferase activity, ChAT; acetylcholinesterase activity, AChE; and sodium-de pendent high affinity choline uptake) in the cortical (CR) and subcortical (SS) regions of the brains of aged (24 month) and young (2 month) rats. Using [3H]-quinuclidinyl benzilate ([3H]-QNB) as the ligand of muscarinic receptor binding, the numbers of mAChR decreased about 30% in both the CR and the SS of aged rats compared with those in young rats, while a significant age-related increase in the affinity of mAChR was observed.[3H]-QNB binding in both the young and aged rat brain was displaced markedly by pirenzepine, while [3H]-QNB binding in the SS of the aged rat brain was displaced at low concentrations of atropine. The Vma, values of ChAT and AChE also decreased about 20-30076 compared with those of young rats. The sodium-dependent high affinity choline uptake was lower in the crude synaptosomal fraction prepared from aged rat brain than in young brain. Hemicholinium-3 inhibited the choline uptake in young rat brain at a concentration range of 1 pM 10 nM, but choline uptake in aged brain was insensitive to hemicholinium-3. These results indicate that natural aging brings about a diffuse and multiple depletion of various biochemical markers in cholinergic neurons.

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Section: Discussionmentioning

confidence: 96%

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confidence: 99%

Age-Related Changes of Cholinergic Markers in the Rat Brain

Yufu

Egashira

Yamanaka

1994

Japanese Journal of Pharmacology

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Co-Dergocrin

Herrschaft¹

1999

Neuro-Psychopharmaka Ein Therapie-Handbuch

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Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus

et al. 1995

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We examined by morphological methodology the effect of (S)-N-ethyl-3-[(1-dimethyl-amino)ethyl]-N-methyl-phenylcarbamate hydrogentartrate (ENA-713), an acetylcholinesterase (AChE) inhibitor, on ischemia-induced neuronal death in the gerbil hippocampus due to a 5-min ligation of bilateral common carotid arteries after light ether anesthesia. Pyramidal cells had been decreased to 27% of sham-operated controls and the number of hypertrophic astrocytes expressing glial fibrillary acidic protein (GFAP) markedly increased in the hippocampal CA1 subfield 14 days after ischemia. However, post-ischemic administration of ENA-713 (three times 0.2 mg/kg, i.p.) significantly ameliorated this ischemia-induced decrease in the number of pyramidal cells by 47% of sham-operated controls, furthermore, it reduced the ischemia-induced accumulation of GFAP-positive astrocyte in the CA1 region. Together with previous results showing that ENA-713 protected against the ischemia-induced cholinergic abnormalities in the gerbil brain and improved cholinergic dysfunctions in the senescent rat brain, our present findings suggest that ENA-713 prove to be useful for treatment with senile dementia such as cerebrovascular dementia.

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Effects of dihydroergotoxine on central cholinergic neuronal systems and discrimination learning test in aged rats

Cited by 16 publications

References 22 publications

Age-Related Changes of Cholinergic Markers in the Rat Brain

Age-Related Changes of Cholinergic Markers in the Rat Brain

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Post-ischemic administration of the acetylcholinesterase inhibitor ENA-713 prevents delayed neuronal death in the gerbil hippocampus

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