Downregulation of complexin I and complexin II in the medial thalamus is blocked by N-acetylcysteine in experimental Wernicke's encephalopathy.

Abstract

Metabolic dysfunction as a consequence of thiamine (vitamin B1) deficiency (TD), a model of Wernicke's encephalopathy, leads to elevation of extracellular glutamate concentration in vulnerable brain regions consistent with the development of excitotoxicity. Complexin I and complexin II are two genes labeling principally inhibitory and excitatory synapses, respectively. Because current evidence supports an important role for complexins in the modulation of neurotransmitter release, we examined the involvement of both proteins in the pathology of the medial thalamus and inferior colliculus in TD rats by immunoblotting. At the symptomatic stage, complexin I and complexin II levels in the medial thalamus were decreased by 63% and 45%, respectively, compared to control animals, but were unchanged in the inferior colliculus. These changes in thalamus were also observed using immunohistochemical methods, and seemed to be due to downregulation of both proteins because synaptophysin levels were unaffected in this brain region. In addition, cotreatment with the antioxidant N- acetylcysteine prevented both neuronal loss and downregulation of complexins. Our findings suggest dysregulation of excitatory and inhibitory neurotransmitter release in the medial thalamus, which is not present in the inferior colliculus. Furthermore, loss of complexin I and II in the thalamus may be mediated by processes that involve oxidative stress. Such changes in complexin levels may contribute to the pathophysiology of thalamic damage in TD, and offer a potential basis for the well-known differences in pathology between this structure and the inferior colliculus in this disorder.

• Authors: Alan S Hazell, Chunlei Wang
• Journal: Journal of neuroscience research (J Neurosci Res) 2005 Jan 1-15 Vol. 79 Issue 1-2 Pg. 200-7 ISSN: 0360-4012 [Print] United States
• PMID: 15573404 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2004 Wiley-Liss, Inc.

Chemical References

• Adaptor Proteins, Vesicular Transport
• Antimetabolites
• Nerve Tissue Proteins
• complexin I
• complexin II
• Pyrithiamine
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Adaptor Proteins, Vesicular Transport
• Animals
• Antimetabolites (metabolism)
• Blotting, Western (methods)
• Disease Models, Animal
• Down-Regulation (drug effects)
• Drug Interactions
• Gene Expression Regulation (drug effects)
• Immunohistochemistry (methods)
• Male
• Nerve Tissue Proteins (metabolism)
• Pyrithiamine (toxicity)
• Rats
• Rats, Sprague-Dawley
• Thalamus (drug effects, metabolism)
• Thiamine Deficiency (complications, metabolism, physiopathology)
• Wernicke Encephalopathy (chemically induced, metabolism, physiopathology)