Second messenger/signal transduction pathways in major mood disorders: Moving from membrane to mechanism of action, part II: bipolar disorder

The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in support of intracellular mediators in the pathophysiology and treatment of preclinical models of despair and major depressive disorder (MDD). More specifically, we will focus on the following pathways: cAMP/PKA/CREB, neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3β, and NFκB/ΔFosB. We will also discuss recent discoveries with rapidly acting antidepressants, which activate the mammalian target of rapamycin (mTOR) and release of inhibition on local translation via elongation factor stimulation. Throughout this discourse, we will highlight potential intracellular targets for therapeutic intervention. Finally, future clinical implications are discussed

Sintered fused silica based composites

In present work, complex mixtures were designed based on fused SiO(2), beta-SiC and different oxide additives. The addition of Al(2)O(3) and mulite - 3Al(2)O(3) 2SiO(2) influence was investigated in order to obtain high temperature strength, thermal shock resistant and corrosion resistant composites. Thermal treatment was conducted in conventionally electric furnace in air and in argon respectively, in the 800-1250 degrees C temperature range. Sintered composites were characterised by bulk density, open porosity, and thermal shock resistance and thermal expansion measurements. The crystalline phase evolution in conjunction with each heat curing procedure was analysed by X-ray diffraction and FTIR spectrometry. Microstructure investigation of sintered samples was carried using scanning and transmission electron microscopy. The relationship between the FTIR spectra and structure of the powders and sintered composites was explained

Sintered fused silica based composites

In present work, complex mixtures were designed based on fused SiO(2), beta-SiC and different oxide additives. The addition of Al(2)O(3) and mulite - 3Al(2)O(3) 2SiO(2) influence was investigated in order to obtain high temperature strength, thermal shock resistant and corrosion resistant composites. Thermal treatment was conducted in conventionally electric furnace in air and in argon respectively, in the 800-1250 degrees C temperature range. Sintered composites were characterised by bulk density, open porosity, and thermal shock resistance and thermal expansion measurements. The crystalline phase evolution in conjunction with each heat curing procedure was analysed by X-ray diffraction and FTIR spectrometry. Microstructure investigation of sintered samples was carried using scanning and transmission electron microscopy. The relationship between the FTIR spectra and structure of the powders and sintered composites was explained

Shank3 as a potential biomarker of antidepressant response to ketamine and its neural correlates in bipolar depression

Shank3, a post-synaptic density protein involved in N-methyl-d-aspartate (NMDA) receptor tethering and dendritic spine rearrangement, is implicated in the pathophysiology of bipolar disorder. We hypothesized that elevated baseline plasma Shank3 levels might predict antidepressant response to the NMDA receptor antagonist ketamine