Inhibition of mitochondrial complex II alters striatal expression of genes involved in glutamatergic and dopaminergic signaling: possible implications for Huntington's …

M Napolitano, D Centonze, P Gubellini, S Rossi… - Neurobiology of …, 2004 - Elsevier
M Napolitano, D Centonze, P Gubellini, S Rossi, S Spiezia, G Bernardi, A Gulino…
Neurobiology of disease, 2004Elsevier
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 …
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.
Elsevier