Abstract
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by motor abnormalities and cognitive impairment. The irreversible succinate dehydrogenase (SD) inhibitor 3-nitropropionic acid (3NP) causes neurodegeration in the striatum resembling HD when administered to rodents or primates. Using corticostriatal brain slice preparations, we analyzed the pattern of gene expression following 3NP application utilizing cDNA microarrays. Acute 3NP treatment modulates the expression of several genes involved in dopaminergic and glutamatergic signaling in corticostriatal brain slices, and unbalances the downstream serine/threonine protein kinase and phosphatase network affecting the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32). Our data provide new information about the molecular events possibly underlying neurodegeneration induced by this mitochondrial toxin.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Dopamine / genetics*
-
Dopamine / metabolism
-
Dopamine and cAMP-Regulated Phosphoprotein 32
-
Electron Transport Complex II / antagonists & inhibitors
-
Electron Transport Complex II / drug effects
-
Electron Transport Complex II / physiology*
-
Enzyme Inhibitors / pharmacology
-
Gene Expression Regulation, Enzymologic / drug effects
-
Gene Expression Regulation, Enzymologic / genetics
-
Glutamic Acid / genetics*
-
Glutamic Acid / metabolism
-
Huntington Disease / genetics*
-
Huntington Disease / metabolism*
-
Huntington Disease / physiopathology
-
In Vitro Techniques
-
Neostriatum / drug effects
-
Neostriatum / metabolism*
-
Neostriatum / physiopathology
-
Nerve Tissue Proteins*
-
Nitro Compounds
-
Oligonucleotide Array Sequence Analysis
-
Phosphoproteins / drug effects
-
Phosphoproteins / metabolism
-
Phosphoric Monoester Hydrolases / antagonists & inhibitors
-
Phosphoric Monoester Hydrolases / metabolism
-
Propionates / pharmacology
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / metabolism
-
Rats
-
Rats, Wistar
-
Signal Transduction / drug effects
-
Signal Transduction / genetics
-
Succinate Dehydrogenase / antagonists & inhibitors
-
Succinate Dehydrogenase / metabolism
Substances
-
Dopamine and cAMP-Regulated Phosphoprotein 32
-
Enzyme Inhibitors
-
Nerve Tissue Proteins
-
Nitro Compounds
-
Phosphoproteins
-
Propionates
-
Glutamic Acid
-
Electron Transport Complex II
-
Succinate Dehydrogenase
-
Protein Serine-Threonine Kinases
-
Phosphoric Monoester Hydrolases
-
3-nitropropionic acid
-
Dopamine