Cortical cholinergic abnormalities contribute to the amnesic state induced by pyrithiamine-induced thiamine deficiency in the rat.

Abstract

Although the key neuropathology associated with diencephalic amnesia is lesions to the thalamus and/or mammillary bodies, functional deactivation of the hippocampus and associated cortical regions also appear to contribute to the memory dysfunction. For example, there is loss of forebrain cholinergic neurons and alterations in stimulated acetylcholine (ACh) levels in the hippocampus and cortex in animal models of diencephalic amnesia associated with thiamine deficiency. In the present study, the pyrithiamine-induced thiamine deficiency rat model was used to assess the functional relationships between thalamic pathology, behavioral impairment, ACh efflux and cholinergic innervation of the hippocampus and cortex. In pyrithiamine-induced thiamine deficiency-treated rats, ACh efflux during behavioral testing was blunted to differing degrees in the hippocampus, medial frontal cortex and retrosplenial cortex. In addition, significant reductions in cholinergic fiber densities were observed in each of these regions. However, only hippocampal cholinergic fiber density correlated significantly with ACh efflux in the same region, suggesting that the reduction in cortical ACh efflux in cases of diencephalic amnesia cannot be fully explained by a loss of cholinergic fiber innervation. This notion supports the emerging theory that the functional consequences of the distal effects of lesions go beyond simple deafferentation. Specifically, some frontal cortical regions exhibit hypersensitivity to deafferentation that is only detected during behavioral and/or physiological demand.

• Authors: Steven Anzalone, Ryan P Vetreno, Raddy L Ramos, Lisa M Savage
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 32 Issue 5 Pg. 847-58 (Sep 2010) ISSN: 1460-9568 [Electronic] France
• PMID: 20726882 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. No claim to original US government works.

Chemical References

• Pyrithiamine
• Acetylcholinesterase
• Acetylcholine

Topics

• Acetylcholine (metabolism)
• Acetylcholinesterase (metabolism)
• Amnesia (chemically induced, metabolism, pathology, physiopathology)
• Animals
• Cerebral Cortex (metabolism, pathology, physiopathology)
• Cholinergic Fibers (pathology)
• Disease Models, Animal
• Hippocampus (metabolism, pathology, physiopathology)
• Male
• Maze Learning (physiology)
• Microdialysis (methods)
• Pyrithiamine
• Rats
• Rats, Sprague-Dawley
• Thiamine Deficiency (chemically induced, metabolism, pathology, physiopathology)