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Current Topics in Pharmacology   Volumes    Volume 14 
Abstract
Selective septohippocampal cholinergic lesioning in rat brain: Effects on muscarinic receptor function and secretase enzyme activity
Vedavalli N. Pokala, Paula A. Witt-Enderby, Robert B. Gibbs, David A. Johnson
Pages: 73 - 78
Number of pages: 6
Current Topics in Pharmacology
Volume 14 

Copyright © 2010 Research Trends. All rights reserved

ABSTRACT
 
Cholinergic hypofunction and the abnormal aggregation and deposition of the amyloid-beta peptide (A-beta) in the brain serve as the central dogma for the pathogenesis and development of the neurodegeneration associated with Alzheimer’s disease (AD) related dementia. A-beta peptide is made by the proteolytic cleavage of amyloid precursor protein (APP) by secretase enzymes. There is evidence that relates cholinergic hypofunction to the amount of A-beta peptide found in the brain of a dementia patient. Current research is focused on further investigating this hypothesis and establishing a connection between cholinergic dysfunction, secretase enzyme levels and A-beta peptide accumulation in the brain. Our research investigates the role of cholinergic hypofunction on the hippocampal muscarinic receptor function and its modulation of the secretase enzyme levels in a 192 IgG Saporin (SAP) lesioned rat model. The results demonstrate that on SAP lesioning directed at the medial septum (MS) there is a significant loss in hippocampal muscarinic receptor function and alpha-secretase levels, an enzyme essential for the formation of neuroprotective sAPPalpha. The results validate the role of muscarinic receptor function on Alpha secretase enzyme activity. In addition, the SAP model established in the lab may also be a useful tool in studying the affects of selective septohippocampal cholinergic hypofunction in dementia.
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