Chronic treatment with lithium or valproate modulates the expression of Homer1b/c and its related genes Shank and Inositol 1,4,5-trisphosphate receptor.

Homer proteins are associated with both dopaminergic and glutamatergic function. In addition, these proteins are implicated in many signal transduction pathways that are also putative targets of the mood stabilizers lithium and valproate (VPA). This study investigated the effect of in vivo chronic administration of therapeutically-relevant doses of lithium and VPA on the expression of the inducible (Homer1a and ania-3) and constitutive (Homer1b/c) isoforms of the Homer1 gene in rat brain, and of two other Homer-related genes: Inositol 1,4,5 trisphosphate receptor (IP3R) and Shank.

Striatal expression of Homer1a is affected by genotype but not dystonic phenotype of tottering mice: a model of spontaneously occurring motor disturbances.

Tottering (tg) mice carry a missense mutation in the gene coding for P/Q-type voltage-dependent Ca(2+) channels (VDCCs). Aberrant functioning of P/Q-type VDCCs results in molecular alterations in Ca(2+) currents and in glutamate and dopamine systems. As a consequence, tottering mice exhibit mild ataxia, spontaneous epilepsy, and paroxysmal dyskinesia.

Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions.

Homer1a and Yotiao are two post-synaptic density proteins at the crossroad of dopamine-glutamate neurotransmission. Homer1a has been implicated in the pathophysiology of schizophrenia and is differentially induced by typical and atypical antipsychotics, perhaps according to their dopaminergic profile. Yotiao has been involved in glutamate and dopamine post-synaptic signalling.

Farnesyl transferase inhibitors induce neuroprotection by inhibiting Ha-Ras signalling pathway.

In previous studies we found that the GTPase p21 Harvey-Ras (Ha-Ras) stimulates the production of reactive oxygen species and induces apoptosis by oxidative stress; this effect was reversed by farnesyl transferase inhibitors (FTIs). In this study we investigated whether FTIs reduce rat brain damage induced by an excitotoxic stimulus, and the signalling pathway(s) underlying the neuroprotection by FTIs. In brain tissue, protein levels of Ha-Ras and farnesylation inhibition were assayed by Western blot, and superoxide production was measured by hydroethidine.

Permanent focal brain ischemia induces isoform-dependent changes in the pattern of Na+/Ca2+ exchanger gene expression in the ischemic core, periinfarct area, and intact brain regions.

Dysregulation of sodium [Na+]i and calcium [Ca2+]i homeostasis plays a pivotal role in the pathophysiology of cerebral ischemia. Three gene products of the sodium-calcium exchanger family NCX1, NCX2, and NCX3 couple, in a bidirectional way, the movement of these ions across the cell membrane during cerebral ischemia. Each isoform displays a selective distribution in the rat brain.