Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors.

Ethnopharmacological Relevance: Withania somnifera (WS) has been traditionally used in Ayurvedic medicine as a remedy for debility, stress, nervous exhaustion, insomnia, loss of memory, and to enhance cognitive function. This study provides an empirical evidence to support the traditional use of WS to aid in mental process engaging GABAergic signaling.

Aim Of The Study: We evaluated the effect of aqueous WS root extract (aqWS), and its two main components, withaferin A and withanolide A, on the main inhibitory receptors in the central nervous system: ionotropic GABAA receptors.

Antidepressants are neuroprotective against nutrient deprivation stress in rat hippocampal neurons.

There is ample evidence that depression and stress can be ameliorated through the use of physical exercise and/or antidepressant drugs. Both have been shown to promote neuroprotection against atrophy of dendrites and neuronal death through the activation of pro-survival signaling pathways, such as that of phosphatidyl inositol 3' kinase (PI-3K) and mitogen-activated protein kinase (MAPK). Depriving neurons in culture of several vital nutrients provides a viable model of neuronal stress, trauma or insult that occurs in vivo.

Norepinephrine and nitric oxide promote cell survival signaling in hippocampal neurons.

Nitric oxide (NO), physical exercise and/or antidepressant drugs, through the increased release of norepinephrine and brain-derived neurotrophic factor (BDNF), have been shown to exert profound protective, pro-survival effects on neurons otherwise compromised by injury, disease, prolonged stress, and subsequent depression in vivo. We sought, therefore, to evaluate such survival and neuroprotection in hippocampal neurons in culture, which, in an analogous model of in vivo cellular stress, was deprived of several vital nutrients. We assessed pro-survival outcomes following the application of norepinephrine or the noradrenergic partial agonist, clonidine, a general nitric oxide synthase inhibitor and NO donor, using a cell survival assay and quantitative Western blotting of the survival signaling molecules, BDNF, P-CREB, P-Akt, and P-MAPK in hippocampal neuronal lysates.

Differential behavioral and neurochemical effects of exercise, reboxetine and citalopram with the forced swim test.

Aims: In this study, we investigated whether short-term exercise, known to promote hippocampal brain-derived neurotrophic factor (BDNF) expression, would also enhance activity in the Porsolt forced swim test (FST), a model for assessing antidepressant efficacy. We also wished to determine whether exercise combined with antidepressants would be more effective at modifying behavior in the FST than either intervention alone. In parallel with this, we also expected that these interventions would preserve post-stress levels of BDNF, and that antidepressants designed to selectively enhance noradrenergic or serotonergic neurotransmission (reboxetine or citalopram, respectively) would have differential effects on behavior and BDNF expression.

Running exercise-induced up-regulation of hippocampal brain-derived neurotrophic factor is CREB-dependent.

The past decade has witnessed burgeoning evidence that antidepressant medications and physical exercise increase the expression of hippocampal brain-derived neurotrophic factor (BDNF). This phenomenon has gained widespread appeal, because BDNF is one of the first macromolecules observed to play a central role not only in the treatment of mood disorders, but also in neuronal survival-, growth-, and plasticity-related signaling cascades. Thus, it has become critical to understand how BDNF synthesis is regulated.