Long-term cholinergic denervation caused by early postnatal AF64A lesion prevents development of Muscarinic receptors in rat hippocampus

P.G.M. Luiten*, E.A. van der Zee, E. Gáspár, B. Buwalda, A.D. Strosberg, C. Nyakas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

The effect of early postnatal (day 8) intracerebroventricular injections of the putative cholinotoxin ethylcholine aziridinium mustard (AF64A) on development of cholinergic innervation and post-synaptic muscarinic acetylcholine receptors in the rat hippocampus was examined. The cholinotoxin applied at this stage of development leads to a permanent denervation of cholinergic fibres in the hippocampus in adulthood demonstrated by (immuno)histochemical methods and biochemical assays. Muscarinic receptor expression in the principal neurons of dentate gyrus and cornu ammonis was strongly reduced as studied by immunostaining with antibodies against muscarinic receptor proteins and binding assays with the muscarinic antagonist quinuclidinyl benzilate. Cholinoceptive interneurons and somatostinergic interneurons are not affected by the developmental cholinergic lesion. Immunoreactivity to protein kinase C type I as a marker for inositolphosphate-related cellular activation systems slightly decreased in the apical dendrites of the hippocampal principal neurons. These findings indicate that damage to ingrowing cholinergic terminals in the hippocampus in the early postnatal period is a critical hazard for development of the muscarinic receptor system in the hippocampal principal neurons. These results are discussed for their significance to the neural mechanisms that underlie perinatal brain damage and associated cognitive dysfunction.

Original languageEnglish
Pages (from-to)131-141
Number of pages11
JournalJournal of Chemical Neuroanatomy
Volume5
Issue number2
DOIs
Publication statusPublished - 1992

Keywords

  • PERINATAL DAMAGE
  • CHOLINERGIC INNERVATION
  • PROTEIN-KINASE-C
  • CENTRAL NERVOUS-SYSTEM
  • AZIRIDINIUM ION AF64A
  • ETHYLCHOLINE AZIRIDINIUM
  • ACETYLCHOLINE-RECEPTOR
  • INTRAVENTRICULAR AF64A
  • CEREBRAL HYPOXIA
  • BASAL FOREBRAIN
  • WORKING MEMORY
  • BINDING-SITES

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