Design and functional evaluation of an optically active μ-opioid receptor.

The use of opioids, which achieve therapeutic analgesia through activation of μ-opioid receptors, are limited in the management of chronic pain by adverse effects including tolerance and addiction. Optogenetics is an emerging approach of designing molecular targets that can produce cell-specific receptor-mediated analgesia with minimal side effects. Here we report the design and functional characterization of a chimeric μ-opioid receptor that could be photoactivated to trigger intracellular signaling.

Animal models of depression and neuroplasticity: assessing drug action in relation to behavior and neurogenesis.

Depression is among the most prevalent forms of mental illness and a major cause of morbidity worldwide. Diagnosis of depression is mainly based on symptomatic criteria, and the heterogeneity of the disease suggests that multiple different biological mechanisms may underlie its etiology. Animal models have been important for recent advances in experimental neuroscience, including modeling of human mood disorders, such as depression and anxiety.

Curcumin prevents corticosterone-induced neurotoxicity and abnormalities of neuroplasticity via 5-HT receptor pathway.

Curcumin, a major active component of Curcuma longa, possesses antioxidant and neuroprotective activities. The present study explores the mechanisms underlying the neuroprotective effect of curcumin against corticosterone and its relation to 5-hydroxy tryptamine (5-HT) receptors. Exposure of cortical neurons to corticosterone results in decreased mRNA levels for three 5-HT receptor subtypes, 5-HT(1A), 5-HT(2A) and 5-HT(4), but 5-HT(1B,) 5-HT(2B), 5-HT(2C), 5-HT(6) and 5-HT(7) receptors remain unchanged.

Antidepressant-like effect of trans-resveratrol: Involvement of serotonin and noradrenaline system.

The antidepressant-like effect of trans-resveratrol, a phenolic compound present in polygonum cuspidatum, was evaluated through behavioral and neurochemical methods. trans-Resveratrol (20, 40 and 80 mg/kg, via gavage) significantly decreased the immobility time in mouse models of despair tests, but did not influence locomotor activity. Two behavioral models and neurochemical assays suggested that trans-resveratrol produced a significant increase in serotonin and noradrenaline levels at 40 or 80 mg/kg in brain regions.

Antidepressant-like effect of low molecular proanthocyanidin in mice: involvement of monoaminergic system.

Proanthocyanidin is a phenolic product present in plants which has antioxidant, antinociceptive and neuroprotective properties, without inducing significant toxicological effects. The present study tested the hypothesis that low molecular proanthocyanidin from grapes that has optimized bioavailability, would exert antidepressant-like activities in behavioral despair tests. The results suggested that oral administration proanthocyanidin at doses of 25 and 50mg/kg for 7days significantly reduced the duration of immobility in both the tail suspension and forced swimming tests.

Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress.

Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously we demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown.

Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats.

Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicine, which has been used to effectively manage stress and depression-related disorders in China. As the active component of curcuma longa, curcumin possesses many therapeutic properties; we have previously described its antidepressant activity in our earlier studies using the chronic unpredictable stress model of depression in rats. Recent studies show that stress-induced damage to hippocampal neurons may contribute to the phathophysiology of depression.