A long-term increase in GAD65 and GAD67 levels was dependent on brain region and treatment period. Vesicular GABA transporter was insensitive to GVG. The overall effect of GVG on the Cl(-) co-transporters NKCC1 and KCC2 was an enhancement of their synthesis, which was dependent on the treatment period and brain region studied. In addition, a short-term
increase was followed by a long-term decrease in KCC2 oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices. Analysis of the Ca(2+) WZB117 ic50 binding proteins expressed in subpopulations of GABAergic cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4-14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in GVG mice compared to controls during this period. Cumulatively, these results suggest MX69 in vitro a particular susceptibility of the hippocampus to GVG when exposed during days P4-14. In conclusion, our studies have identified modifications of key components in the inhibitory system during a critical developmental period. These
findings provide novel insights into the deleterious consequences observed in children following prenatal and neonatal exposure to GABA-potentiating drugs. Neuropsychopharmacology (2010) 35, 1138-1154; doi: 10.1038/npp.2009.219; published online 30 December 2009″
“Tardive dyskinesia (TD) is characterized by repetitive, involuntary, and purposeless Smoothened movements that develop in patients treated with long-term dopaminergic antagonists, usually antipsychotics. By a genome-wide association screening of TD in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD (non-TD group) and subsequent confirmation in independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we identified association of a single nucleotide polymorphism, rs2445142, (allelic p = 2 x 10(-5)) in the HSPG2
(heparan sulfate proteoglycan 2, perlecan) gene with TD. The risk allele was significantly associated with higher expression of HSPG2 in postmortem human prefrontal brain (p<0.01). Administration of daily injection of haloperidol (HDL) for 50 weeks significantly reduced Hspg2 expression in mouse brains (p<0.001). Vacuous chewing movements (VCMs) induced by 7-week injection of haloperidol-reserpine were significantly infrequent in adult Hspg2 hetero-knockout mice compared with wild-type littermates (p<0.001). Treatment by the acetylcholinesterase inhibitor, physostigmine, was significantly effective for reduction of VCMs in wild-type mice but not in Hspg2 hetero-knockout mice. These findings suggest that the HSPG2 gene is involved in neuroleptic-induced TD and higher expression of HSPG2, probably even after antipsychotic treatment, and may be associated with TD susceptibility. Neuropsychopharmacology (2010) 35, 1155-1164; doi: 10.1038/npp.2009.