Increased cell proliferation (BrdU incorporation) in subgranular zone (SGZ) was achieved after chronic treatment with a high dose (40 mg/kg/day) of venlafaxine. However, significant increases in the immunoreactivity of hippocampal beta-catenin

in SGZ were already detected after administration of a lower dose of the drug (10 mg/kg/day). Western blot and immunoelectron microscopy studies demonstrated an increased presence of beta-catenin at the nuclear level. An increase in cytosolic AKT levels was also observed in venlafaxine-treated animals. These Selleckchem BX-795 results suggest that the hippocampal proliferative effect of chronic venlafaxine, only evident when both serotonin (5-HT) and noradrenaline/norepinephrine (NE) reuptake systems are inhibited, requires a strong activation of intracellular signaling through Wnt (beta-catenin translocation) and AKT/PKB pathways. This activation AZD5363 mw would probably result in an increase of the expression of cell cycle regulator genes. Furthermore pERK2/ERK2 rate was also increased in the hippocampus of AD-treated animals, while no differences in the levels of CREB and p-CREB were observed. These results illustrate the complexity of the intracellular events underlying the neurogenetic responses of ADs. They also support the relevance of such effects for the therapeutic effects of

these drugs. (c) 2008 Elsevier Ltd. All rights reserved.”
“Purpose: We studied the effects of long-term fructose feeding and metabolic perturbations on bladder function

in rats.

Materials and Methods: Female Wistar rats were fed a fructose enriched (60%) or control diet for 3 and 6 months. In vitro contractile responses to electrical field stimulation, KCl, carbachol and adenosine triphosphate, and in vivo cystometry were used to evaluate selleck kinase inhibitor bladder function. Tissue staining and electron microscopy were also performed to evaluate the structural changes in rats subjected to metabolic syndrome. Biochemical and physiological data were compared between fructose fed rats and age matched controls.

Results: All rats fed a fructose enriched diet for 3 months showed insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension. These fructose fed rats showed a decreased contractile response to high concentrations of KCl but not to other parameters tested compared to controls. Eight of the 12 rats (66.7%) showed abnormal cystometry, mainly by increased phasic contractions. In 6-month fructose fed rats contractile responses to electrical field stimulation, KCl and carbachol were decreased significantly. However, responsiveness to high concentrations of adenosine triphosphate was significantly increased. Morphological studies in fructose fed rats showed swollen mitochondria in bladder smooth muscle, increased leukocyte infiltration between interstitial tissue and neutrophil adhesion around the endothelium of vessels.