HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Changes in cortical acetyl-CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG-saporin.

Abstract
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 Ca2+-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.
AuthorsMaria Tomaszewicz, Steffen Rossner, Reinhard Schliebs, Justyna Cwikowska, Andrzej Szutowicz
JournalJournal of neurochemistry (J Neurochem) Vol. 87 Issue 2 Pg. 318-24 (Oct 2003) ISSN: 0022-3042 [Print] England
PMID14511109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 192 IgG-saporin
  • Antibodies, Monoclonal
  • Cholinergic Agents
  • Immunotoxins
  • Ribosome Inactivating Proteins, Type 1
  • Acetyl Coenzyme A
  • N-Glycosyl Hydrolases
  • Saporins
  • Acetylcholine
Topics
  • Acetyl Coenzyme A (metabolism)
  • Acetylcholine (metabolism)
  • Animals
  • Antibodies, Monoclonal
  • Brain Chemistry
  • Cerebral Cortex (chemistry, drug effects, metabolism)
  • Cholinergic Agents
  • Denervation (methods)
  • Immunotoxins
  • Male
  • Mitochondria (chemistry, drug effects, metabolism)
  • N-Glycosyl Hydrolases
  • Neurodegenerative Diseases (chemically induced, metabolism)
  • Prosencephalon (chemistry, drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Synaptosomes (chemistry, drug effects, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: