Selective presynaptic cholinergic neurotoxicity following intrahippocampal AF64A injection in rats.

Abstract:

:Compound AF64A, ethylcholine mustard aziridinium ion (0.4-8 nmol) was stereotaxically administered into rat dorsal hippocampus, and neurochemical changes were determined 5 days later. AF64A treatment, over an almost 10-fold dose range, resulted in a significant (up to 70%) decline in choline acetyltransferase activity. In the same tissue samples, Na+-dependent choline transport activity was also lowered, with most decreases ranging between 10 and 50% of controls; however, there was no significant correlation (r = 0.39) between these two parameters. Acetylcholinesterase activity was not affected by AF64A treatment when assayed by either histochemical or enzymatic methods. AF64A reduced acetylcholine levels by 43%, but did not alter norepinephrine content or serotonin uptake. These results demonstrate that AF64A can induce a specific, long-term reduction of cholinergic presynaptic biochemical markers in rat hippocampus. Thus, AF64A can serve as a useful new tool to study the cholinergic system and as an important agent to help develop animal models representing disorders of central cholinergic hypofunction.

journal_name

J Neurochem

authors

Mantione CR,Zigmond MJ,Fisher A,Hanin I

doi

10.1111/j.1471-4159.1983.tb11836.x

subject

Has Abstract

pub_date

1983-07-01 00:00:00

pages

251-5

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

41

pub_type

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