Differential long-term effect of AF64A on [3H]ACh synthesis and release in rat hippocampal synaptosomes

Zipora Pittel, Sasson Cohen, Abraham Fisher, Eliahu Heldman

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 μl/side) or vehicle (saline). Synaptosomes were preloaded with [3H]choline ([3H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [3H]Ch and [3H]acetylcholine ([3H]ACh) and for their ability to synthesize and release [3H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [3H]ACh was reduced to 60% of control; (ii) residing [3H]ACh levels were 43% of control while residing [3H]Ch levels were 72% of control; (iii) basal and K+-induced [3H]ACh release were 77% and 73% of control, respectively; (iv) high K+-induced synthesis of [3H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons.

Original languageEnglish
Pages (from-to)148-151
Number of pages4
JournalBrain Research
Volume586
Issue number1
DOIs
StatePublished - 17 Jul 1992
Externally publishedYes

Keywords

  • AF64A
  • Acetylcholine release
  • Acetylcholine synthesis
  • Cholinergic dysfunction
  • Cholinergic toxicity

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