Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia.

Background: Schizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion.

Studies in humans and mice implicate neurocan in the etiology of mania.

Objective: Genome-wide association has been reported between the NCAN gene and bipolar disorder. The aims of this study were to characterize the clinical symptomatology most strongly influenced by NCAN and to explore the behavioral phenotype of Ncan knockout (Ncan(-/-)) mice.

Method: Genotype/phenotype correlations were investigated in patients with bipolar disorder (N=641) and the genetically related disorders major depression (N=597) and schizophrenia (N=480).

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls.

Haploinsufficiency of the murine polycomb gene Suz12 results in diverse malformations of the brain and neural tube.

Polycomb proteins are epigenetic regulators of gene expression. Human central nervous system (CNS) malformations are congenital defects of the brain and spinal cord. One example of a human CNS malformation is Chiari malformation (CM), which presents as abnormal brainstem growth and cerebellar herniation, sometimes accompanied by spina bifida and cortical defects; it can occur in families.

Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis.

The regeneration of diseased hyaline cartilage continues to be a great challenge, mainly because degeneration--caused either by major injury or by age-related processes--can overextend the tissue's self-renewal capacity. We show that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). These exhibit stem cell characteristics such as clonogenicity, multipotency, and migratory activity.

Antagonism between DNA and H3K27 methylation at the imprinted Rasgrf1 locus.

At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other.

Differential distribution of PDE4B splice variant mRNAs in rat brain and the effects of systemic administration of LPS in their expression.

Phosphodiesterases (PDE) control intracellular cyclic adenosine monophosphate (cAMP) levels, which appear to play an important role in the regulation of inflammation. PDE4B is especially important in this process. Using in situ hybridization histochemistry we first mapped the expression sites of the four PDE4B splicing forms in rat brain.

Regulation of cAMP phosphodiesterase mRNAs expression in rat brain by acute and chronic fluoxetine treatment. An in situ hybridization study.

Changes in brain cyclic AMP (cAMP) have been suggested to underlie the clinical action of antidepressant treatments. Also, a regionally-selective regulation of cAMP-specific phosphodiesterases (PDEs) has been demonstrated for some antidepressants. To further investigate the effects of antidepressant treatments on PDEs, we examined the expression of different cAMP-specific PDEs in the brain of rats treated (1 and 14 days) with fluoxetine 3 mg/kg day.

Differential distribution of PDE4D splice variant mRNAs in rat brain suggests association with specific pathways and presynaptical localization.

cAMP plays an important role as a second-messenger molecule controlling multiple cellular processes. Its hydrolysis provides an important mechanism by which cAMP levels are regulated. This is performed by a large multigene family of cyclic nucleotide phosphodiesterases (PDEs).