Altered expression of hippocampal dentate granule neuron genes in a mouse model of human 22q11 deletion syndrome.

Hemizygous deletion of a 3 Mb region of 22q11.2 is found in 1/4000 humans and produces 22q11 deletion syndrome (22q11DS). Up to 35% of 22q11DS patients develop schizophrenia, making it the second highest risk factor for schizophrenia.

Early changes in Huntington's disease patient brains involve alterations in cytoskeletal and synaptic elements.

Huntington's disease (HD) is caused by a polyglutamine repeat expansion in the N-terminus of the huntingtin protein. Huntingtin is normally present in the cytoplasm where it may interact with structural and synaptic elements. The mechanism of HD pathogenesis remains unknown but studies indicate a toxic gain-of-function possibly through aberrant protein interactions.

Comparison of microarray-based mRNA profiling technologies for identification of psychiatric disease and drug signatures.

The gene expression profiles of human postmortem parietal and prefrontal cortex samples of normal controls and patients with bipolar disease, or human neuroblastoma flat (NBFL) cells treated with the mood-stabilizing drug, valproate, were used to compare the performance of Affymetrix oligonucleotide U133A GeneChips and Agilent Human 1 cDNA microarrays. Among those genes represented on both platforms, the oligo array identified 26-53% more differentially expressed genes compared to the cDNA array in the three experiments, when identical fold change and t-test criteria were applied. The increased sensitivity was primarily the result of more robust fold changes measured by the oligonucleotide system.

Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways.

Electroconvulsive therapy (ECT) remains the treatment of choice for drug-resistant patients with depressive disorders, yet the mechanism for its efficacy remains unknown. Gene transcription changes were measured in the frontal cortex and hippocampus of rats subjected to sham seizures or to 1 or 10 electroconvulsive seizures (ECS), a model of ECT. Among the 3500-4400 RNA sequences detected in each sample, ECS increased by 1.

Overexpression and nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase in a transgenic mouse model of Huntington's disease.

Huntington's disease is due to an expansion of CAG repeats in the huntingtin gene. Huntingtin interacts with several proteins including glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We performed immunohistochemical analysis of GAPDH expression in the brains of transgenic mice carrying the huntingtin gene with 89 CAG repeats.

PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains.

Huntington's disease (HD) is caused by a pathological expansion of a CAG repeat in the first exon of the gene coding for huntingtin, resulting in an abnormally long polyglutamine stretch. Despite its widespread expression, mutant huntingtin leads to selective neuronal loss in the striatum and cortex. Here we report that the neurospecific phosphoprotein PACSIN 1, which has been implicated as playing a central role in synaptic vesicle recycling, interacts with huntingtin via its C-terminal SH3 domain.

Excitotoxic and metabolic damage to the rodent striatum: role of the P75 neurotrophin receptor and glial progenitors.

After injury, the striatum displays several morphologic responses that may play a role in both regenerative and degenerative events. One such response is the de novo expression of the low-affinity p75 neurotrophin receptor (p75(NTR)), a gene that plays critical roles in central nervous system (CNS) cell death pathways. The present series of experiments sought to elucidate the cellular origins of this p75(NTR) response, to define the conditions under which p75(NTR) is expressed after striatal injury, and how this receptor expression is associated with neuronal plasticity.