Histone deacetylase-3 interacts with ataxin-7 and is altered in a spinocerebellar ataxia type 7 mouse model.

Spinocerebellar ataxia type 7 (SCA7) is caused by a toxic polyglutamine (polyQ) expansion in the N-terminus of the protein ataxin-7. Ataxin-7 has a known function in the histone acetylase complex, Spt/Ada/Gcn5 acetylase (STAGA) chromatin-remodeling complex. We hypothesized that some histone deacetylase (HDAC) family members would impact the posttranslational modification of normal and expanded ataxin-7 and possibly modulate ataxin-7 function or neurotoxicity associated with the polyQ expansion.

Gene-microRNA interactions associated with antipsychotic mechanisms and the metabolic side effects of olanzapine.

Rationale: Changes in the cortical expression of small non-coding microRNA (miRNA) have been observed in postmortem analysis of psychotic disorders. Antipsychotic drugs (APDs) are the most effective treatment option for these disorders and have been associated with changes in gene expression. MicroRNA regulate numerous genes involved in brain development and function.

Expression of NPAS3 in the human cortex and evidence of its posttranscriptional regulation by miR-17 during development, with implications for schizophrenia.

NPAS3 is a developmentally important transcription factor that has been associated with psychiatric illness. Our aim is to better define the regulation of NPAS3 mRNA (messenger RNA) levels during normal human prefrontal cortical development and in schizophrenia. Utilizing postmortem tissue from 134 human brains, we assessed: 60 normal brains ranging in age from birth to adulthood, 37 chronic individuals with schizophrenia, and 37 matched controls.

Developmental co-regulation of the beta and gamma GABAA receptor subunits with distinct alpha subunits in the human dorsolateral prefrontal cortex.

The GABA(A) receptor (GABA(A)R) is a pentameric chloride ion channel that mediates neuronal inhibition and is commonly comprised of 2alpha, 2beta and 1gamma subunits. These subunits have distinct characteristics that critically impact receptor function. In this study, we sought to determine if developmental expression of the beta and gamma subunit mRNAs in the prefrontal cortex would show complementary or opposing patterns of change as compared to the alpha subunits.

Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia.

Cortical GABA deficits that are consistently reported in schizophrenia may reflect an etiology of failed normal postnatal neurotransmitter maturation. Previous studies have found prefrontal cortical GABA(A) receptor alpha subunit alterations in schizophrenia, yet their relationship to normal developmental expression profiles in the human cortex has not been determined. The aim of this study was to quantify GABA(A) receptor alpha-subunit mRNA expression patterns in human dorsolateral prefrontal cortex (DLPFC) during normal postnatal development and in schizophrenia cases compared to controls.

K(v) channel interacting protein 3 expression and regulation by haloperidol in midbrain dopaminergic neurons.

Antipsychotic drugs are the main treatment for schizophrenia, despite their adverse side effects and uncertain mode of action. Gene expression studies in the brains of rodents treated with antipsychotic drugs aim to uncover this mechanism and elucidate more specific targets for schizophrenia treatment. Previous expression profiling analyses showed that K(v) channel interacting protein 3 (KChIP3) was down-regulated in the mouse brain following treatment with multiple antipsychotic drugs.

Coregulation of genes in the mouse brain following treatment with clozapine, haloperidol, or olanzapine implicates altered potassium channel subunit expression in the mechanism of antipsychotic drug action.

Background: Antipsychotic drugs are the most effective treatment for the psychotic symptoms of schizophrenia, yet their mechanism of action remains largely unknown.

Objectives: Earlier studies have shown gene expression changes in rodent brains after treatment with antipsychotic drugs. We aimed to further characterize these changes using whole-genome transcript profiling to explore coregulation of genes after multiple antipsychotic drug treatment studies.