Induction of the Wnt antagonist Dickkopf-1 is involved in stress-induced hippocampal damage.

The identification of mechanisms that mediate stress-induced hippocampal damage may shed new light into the pathophysiology of depressive disorders and provide new targets for therapeutic intervention. We focused on the secreted glycoprotein Dickkopf-1 (Dkk-1), an inhibitor of the canonical Wnt pathway, involved in neurodegeneration. Mice exposed to mild restraint stress showed increased hippocampal levels of Dkk-1 and reduced expression of β-catenin, an intracellular protein positively regulated by the canonical Wnt signalling pathway.

The Wnt antagonist, Dickkopf-1, as a target for the treatment of neurodegenerative disorders.

The canonical Wnt pathway contributes to the regulation of neuronal survival and homeostasis in the CNS. Recent evidence suggests that an increased expression of Dickkopf-1 (Dkk-1), a secreted protein that negatively modulates the canonical Wnt pathway, is causally related to processes of neurodegeneration in a number of CNS disorders, including Alzheimer's disease (AD), brain ischemia and temporal lobe epilepsy (TLE). Dkk-1 induction precedes neuronal death in cellular and animal models of excitotoxicity, beta-amyloid toxicity, transient global ischemia, and kainate-induced epilepsy.

Metabotropic glutamate receptors in stem/progenitor cells.

Functional mGlu receptor subtypes are found in stem/progenitor cells, and regulate proliferation, differentiation, and survival of these cells. Activation of mGlu5 receptors supports self-renewal of embryonic stem cells, which are pluripotent cells isolated from the blastocyst capable of generating all the body's cell lineages, including germ cells. Differentiation of embryonic stem cells into embryoid bodies is associated with the induction of mGlu4 receptors, the activation of which drives cell differentiation towards the mesoderm and endoderm lineages.

Characterization of 37 breed-specific single-nucleotide polymorphisms in sheep.

We identified 37 single-nucleotide polymorphisms (SNPs) in sheep and screened 16 individuals from 8 different sheep breeds selected throughout Europe. Population genetic measures based on the genotyping of about 30 sheep from the same 8 breeds are reported. To date, there are no sheep SNPs documented in the National Center for Biotechnology Information dbSNP database.

Context-dependent regulation of embryonic stem cell differentiation by mGlu4 metabotropic glutamate receptors.

The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed by mouse embryonic stem (ES) cells grown under non-differentiating conditions [Cappuccio, I., Spinanti, P. Porcellini, A.

Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells.

Cultured mouse embryonic stem (ES) cells maintained under undifferentiated conditions (i.e. grown in medium containing 15% FCS and leukemia inhibitory factor--LIF) expressed mGlu5 metabotropic glutamate receptors.

Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is required for the development of ischemic neuronal death.

Expression of Dickkopf-1 (Dkk-1), a secreted protein that negatively modulates the Wnt pathway, was induced in the hippocampus of gerbils and rats subjected to transient global cerebral ischemia as well as in cultured cortical neurons challenged with an excitotoxic pulse. In ischemic animals, the temporal and regional pattern of Dkk-1 expression correlated with the profile of neuronal death, as assessed by Nissl staining and Dkk-1 immunostaining in adjacent hippocampal sections. Treatment of ischemic animals with either Dkk-1 antisense oligonucleotides or lithium ions (which rescue the Wnt pathway acting downstream of the Dkk-1 blockade) protected vulnerable hippocampal neurons against ischemic damage.

Ischemic preconditioning: neuronal survival in the face of caspase-3 activation.

Apoptosis is an evolutionarily conserved process critical to tissue development and tissue homeostasis in eukaryotic organisms and, when dysregulated, causes inappropriate cell death. Global ischemia is a neuronal insult that induces delayed cell death with many features of apoptosis. Ischemic preconditioning affords robust protection of CA1 neurons against a subsequent severe ischemic challenge.

Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage.

We examined the expression of metabotropic glutamate (mGlu) receptors in species of fish that differ for their vulnerability to anoxic brain damage. Although expression of mGlu1a and mGlu5 receptors was similar in the brain of all species examined, expression of mGlu2/3 receptors was substantially higher in the brain of anoxia-tolerant species (i.e.

A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity.

We report the identification of a novel rat cDNA encoding a peptide homologous to Humanin, a secreted peptide that specifically protects against neuronal cell death induced by beta-amyloid peptide (Ab) or by mutations causing early-onset familial Alzheimer's disease. The rat gene, which we termed Rattin, encodes a peptide of 38 residues (15 residues longer than Humanin) showing 73% identity in the conserved region to Humanin. The expression profile of the 1.