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. (C) 2004 Elsevier Inc. All rights reserved.
Inhibition of mitochondrial complex II alters striatal expression of genes involved in glutamatergic and dopaminergic signaling: possible implications for Huntington's disease / Napolitano, Maddalena; Diego, Centonze; Paolo, Gubellini; Silvia, Rossi; Stefania, Spiezia; Giorgio, Bernardi; Alberto, Gulino; Paolo, Calabresi. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - STAMPA. - 15:2(2004), pp. 407-414. [10.1016/j.nbd.2003.11.021]
Inhibition of mitochondrial complex II alters striatal expression of genes involved in glutamatergic and dopaminergic signaling: possible implications for Huntington's disease
NAPOLITANO, Maddalena;
2004
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. (C) 2004 Elsevier Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
