Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 336; no. 1; pp. 64 - 76
• Main Authors: Kleiman, Robin J, Kimmel, Lida H, Bove, Susan E, Lanz, Thomas A, Harms, John F, Romegialli, Alison, Miller, Kenneth S, Willis, Amy, des Etages, Shelley, Kuhn, Max, Schmidt, Christopher J
• Format: Journal Article
• Language: English
• Published: United States 01.01.2011
• Subjects: Animals; Corpus Striatum - drug effects; Corpus Striatum - enzymology; Corpus Striatum - metabolism; Disease Models, Animal; Gene Expression Profiling - methods; Gene Expression Regulation - drug effects; Huntington Disease - drug therapy; Huntington Disease - enzymology; Huntington Disease - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurotransmitter Agents - antagonists & inhibitors; Neurotransmitter Agents - biosynthesis; Neurotransmitter Agents - genetics; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Phosphoric Diester Hydrolases - deficiency; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Quinolines - pharmacology; Quinolines - therapeutic use; Signal Transduction - drug effects; Signal Transduction - genetics

Inhibition of phosphodiesterase 10A (PDE10A) promotes cyclic nucleotide signaling, increases striatal activation, and decreases behavioral activity. Enhanced cyclic nucleotide signaling is a well established route to producing changes in gene expression. We hypothesized that chronic suppression of P...