AF64A, a cholinergic neurotoxin, selectively depletes acetylcholine in hippocampus and cortex, and produces long-term passive avoidance and radial-arm maze deficits in the rat

Walsh, Thomas J.; Tilson, Hugh A.; DeHaven, Diane L.; Mailman, Richard B.; Fisher, Abraham; Hanin, Israel

doi:10.1016/0006-8993(84)90684-x

Cited by 215 publications

(34 citation statements)

References 46 publications

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“…AF64A has been shown to cause selective degeneration of cholinergic neurones in the central nervous system (Fisher & Hanin, 1980;Fisher et al, 1982;Mantione et al, 1983b;Sandberg et al, 1984;Walsh et al, 1984). One of its main effects is thought to be inhibition of the high affinity choline uptake system at the nerve terminals (Rylett & Colhoun, 1980;Mantione et al, 1981;Fisher et al, 1982;Curti & Marchbanks, 1984).…”

Section: Discussionmentioning

confidence: 99%

Differences in control of descending inhibition in the proximal and distal regions of rat colon

Hata

Kataoka

Takeuchi

et al. 1990

British J Pharmacology

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Descending inhibition in the proximal and distal portions of rat colon was studied separately, in vitro. In the proximal colon, localized distension with a small balloon caused three types of response (contraction; relaxation; relaxation, then contraction) of the circular muscle on the anal side of the distended region. Distension caused descending relaxation of circular muscle in all segments of the proximal colon, although for this prostaglandin F2α (PGF2α) was necessary in some segments to increase muscle tone. Atropine and guanethidine did not inhibit this descending relaxation, but tetrodotoxin did. Hexamethonium inhibited the descending relaxation in 14 of 17 preparations of proximal colon tested, but not in the others. In the distal colon, distension consistently caused an increase in the tone of the circular muscles. Descending relaxation was observed only after development of higher tone. Atropine and guanethidine did not inhibit the relaxation, but tetrodotoxin did. Hexamethonium did not inhibit the descending relaxation in most of the preparations of distal colon examined. AF64A, an inhibitor of choline uptake, inhibited the response mediated by cholinergic neurones in vitro to electrical transmural stimulation of the longitudinal muscle of proximal colon. Treatment of colonic preparations with AF64A in vitro resulted in inhibition of descending relaxation in those of proximal, but not those of distal, colon. The participation of intrinsic cholinergic neurones in the descending neuronal pathway is strongly suggested by the results in the proximal colon, but less so in the distal colon. The tone and spontaneous contractile activity of colonic circular muscles are discussed in relation to their neuronal control.

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Section: Discussionmentioning

confidence: 99%

Differences in control of descending inhibition in the proximal and distal regions of rat colon

Hata

Kataoka

Takeuchi

et al. 1990

British J Pharmacology

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“…The improvement of biochemical cholin ergic deficits such as that induced by scopol amine [24] or by another cholinotoxin, AF64A [27], in animal model systems can result in improvement in the corresponding behavioral deficits in learning and memory. Such observations have provided the basis for the use of these experimental procedures as models for memory and learning disor ders in humans, such as SDAT.…”

Section: Discussionmentioning

confidence: 99%

Effects of Ginsenoside Rbi on Central Cholinergic Metabolism

Benishin¹,

et al. 1991

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Ginsenosides, the saponins of ginseng, are bioactive ingredients which exert many beneficial effects. One ginsenoside, Rb₁, extracted from North American ginseng (Panax quinquefolium L.), partially prevents the memory deficits induced by a cholinergic agent (scopolamine) in rats. In vitro studies show that Rb₁ has no effect on quinuclidinyl benzylate binding or on acetylcholinesterase activity, but facilitates the release of acetylcholine (ACh) from hippocampal slices. The increase in ACh release is associated with an increased uptake of choline into nerve endings; however, calcium influx is unaltered. The ability of Rb₁ to prevent memory deficits may be related to facilitation of ACh metabolism in the central nervous system.

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“…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). Electrolytic or neurotoxic lesions of the nucleus basalis magnocellularis (NBM) reduce cortical ChAT activity, AChE activity, acetylcholine (ACh) release and choline uptake (21)(22)(23). Moreover, NBM-lesioned rats showed impaired acquisition of a passive avoidance response (24).…”

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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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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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AF64A, a cholinergic neurotoxin, selectively depletes acetylcholine in hippocampus and cortex, and produces long-term passive avoidance and radial-arm maze deficits in the rat

Cited by 215 publications

References 46 publications

Differences in control of descending inhibition in the proximal and distal regions of rat colon

Differences in control of descending inhibition in the proximal and distal regions of rat colon

Effects of Ginsenoside Rbi on Central Cholinergic Metabolism

Age-Related Changes of Cholinergic Markers in the Rat Brain

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