Polymorphisms in the neuronal isoform of tryptophan hydroxylase 2 are associated with bipolar disorder in French Canadian pedigrees.

Objective: Tryptophan hydroxylase is the rate-limiting enzyme in the serotonin biosynthetic pathway and plays an important role in the regulation of serotonin levels. Recently, a brain-specific isoform, tryptophan hydroxylase 2 or n-tryptophan hydroxylase, has been discovered. Some studies reported genetic and functional associations between this isoform and bipolar disorder and/or major depressive disorder.

A genome-wide scan points to a susceptibility locus for bipolar disorder on chromosome 12.

Our previous results pointed to a putative gene for susceptibility to bipolar affective disorder located on the chromosomal region 12q23-q24 that segregated in the Saguenay-Lac-St-Jean population of Quebec. We report here results from a second genome-wide scan based on the analysis of 380 polymorphic microsatellite markers. For the purpose of this analysis, an additional 18 families were recruited from the Saguenay-Lac-St-Jean region and pooled to our previous sample to improve its statistical power, giving a total of 394 sampled individuals.

The C. elegans gene pme-5: molecular cloning and role in the DNA-damage response of a tankyrase orthologue.

Tankyrases are recently identified proteins characterized by ankyrin repeats and a poly(ADP-ribose) polymerase (PARP) signature motif. In vertebrates, tankyrases mediate protein-protein interactions via the ankyrin domain. Many partners have been identified that could function in telomere maintenance, signal transduction in vesicular transport, and cell death.

Intranasal herpes simplex virus type 2 inoculation causes a profound thymidine kinase dependent cerebral inflammatory response in the mouse hindbrain.

The herpes simplex virus (HSV) has the ability to replicate in the central nervous system (CNS), which may cause fatal encephalitis. The present study investigated the activity of the nuclear factor kappa B (NF-kappa B) and the pattern of cytokine/chemokine gene expression across the brain of HSV-infected mice and the role of the viral thymidine kinase (TK) in mediating these effects. Mice were killed 1-8 days after intranasal inoculation with either HSV-2 TK-competent or TK-deficient clinical isolates.

Influence of adrenal glands on the modulation of prolactin gene expression by the endogenous benzodiazepine ligand octadecaneuropeptide in the male rat pituitary gland.

Recently, an 86-amino acid polypeptide with high affinity for diazepam binding sites, termed diazepam-binding inhibitor (DBI), has been found in the rat brain. DBI, as well as a peptide derived from DBI, the octadecaneuropeptide DBI[33-50] (ODN), interacts with the GABA(A) receptor complex. To investigate the role of these endogenous ligands for GABA(A) receptors on prolactin gene expression, we studied the effects of acute intracerebroventricular administration (4 h before sacrifice) of ODN on prolactin mRNA levels in the male rat.

Regulation of the human P450scc gene by steroidogenic factor 1 is mediated by CBP/p300.

Regulation of the human CYP11A gene encoding cytochrome P450scc, which catalyzes the first step of steroid synthesis, is regulated by many trans-acting transcription factors including steroidogenic factor 1 (SF-1). Transfection experiments in human adrenal NCI-H295 cells demonstrate regulation of the P450scc gene promoter region that contains several putative SF-1 binding sites. Cotransfection of SF-1 with a luciferase reporter construct containing the P450scc gene 5'-flanking region from nucleotides -1676 to +49 increased promoter activity, and deletion of the nucleotide sequence from position -1676 to -1620, which removes a putative cAMP response element (CRE), did not affect the stimulatory response to SF-1.

Hyperinsulinemia and abdominal obesity affect the expression of hypertriglyceridemia in heterozygous familial lipoprotein lipase deficiency.

We have reported three missense mutations (G188E, P207L, and D250N) in the lipoprotein lipase (LPL) gene among French-Canadians, resulting in the absence of measurable postheparin plasma LPL activity in homozygotes. Presence of triglyceride- and cholesterol-rich VLDL, as well as cholesterol-poor HDL particles, has been shown in heterozygotes affected by partial reduction in postheparin LPL activity. However, significant heterogeneity in their plasma triglyceride levels has been found, even among individuals carrying the same LPL gene mutation, indicating that factors other than LPL deficiency could affect the phenotypic expression of hypertriglyceridemia in the heterozygous state.

Influence of interleukin-6 on neural activity and transcription of the gene encoding corticotrophin-releasing factor in the rat brain: an effect depending upon the route of administration.

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by various lymphoid and neural cells. In addition to its classic role during immune and inflammatory responses, IL-6 acts on the central nervous system to elicit changes, such as activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effects of systemic and central injection of IL-6 on neural activity and transcription of the corticotrophin-releasing factor (CRF) gene in the brain of conscious rats.