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Changes in cortical acetyl‐CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG‐saporin
Author(s) -
Tomaszewicz Maria,
Roßner Steffen,
Schliebs Reinhard,
Ćwikowska Justyna,
Szutowicz Andrzej
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01983.x
Subject(s) - cholinergic , cholinergic neuron , basal forebrain , choline acetyltransferase , endocrinology , medicine , mitochondrion , acetylcholine , atp citrate lyase , acetylcholinesterase , acetyl coa , biology , chemistry , pyruvate dehydrogenase complex , biochemistry , metabolism , citrate synthase , enzyme
Summary The aim of the present study was to reveal whether reduced cortical cholinergic input affects the acetyl‐CoA metabolism in cholinoceptive cortical target regions which may play a causative role for the deficits in cerebral glucose metabolism observed in Alzheimer's disease. The effect of cortical cholinergic denervation produced by a single intracerebroventricular application of the cholinergic immunotoxin 192IgG‐saporin, on activities of pyruvate dehydrogenase and adenosine triphosphate (ATP)‐citrate lyase as well as on the level of synaptoplasmic and mitochondrial acetyl‐CoA and acetylcholine release in cortical target regions was studied. Cholinergic lesion produced 83%, 72% and 32% decreases in the activities of choline acetyltransferase, acetylcholinesterase and ATP‐citrate lyase in nerve terminals isolated from rat brain cortex, respectively, but no change in pyruvate dehydrogenase activity. Spontaneous and Ca 2+ ‐evoked acetylcholine release from synaptosomes was inhibited by 76% and 73%, respectively, following immunolesion. The lesion‐induced 39% decrease of acetyl‐CoA level in synaptosomal mitochondria was accompanied by 74% increase in synaptoplasmic fraction. Levels of acetyl‐CoA and CoASH assayed in fraction of whole brain mitochondria from lesioned cortex were 61% and 48%, respectively, higher as compared to controls. The data suggest a preferential localization of ATP‐citrate lyase in cholinergic nerve terminals, where it may contribute to the transport of acetyl‐CoA from the mitochondrial to the cytoplasmic compartment. They provide evidence on differential distribution of acetyl‐CoA in subcellular compartments of cholinergic and non‐cholinergic nerve terminals. There are also indications that cholinergic activity affects acetyl‐CoA level and its intracellular distribution in glial and other non‐cholinergic cortical cells.