Activity-dependent changes in synaptic structure and spine morphology are required for learning and memory, and depend on protein translation. We show that the kinase for eukaryotic elongation factor 2 (eEF2K) regulates dendritic spine stability and synaptic structure by modulating activity-dependent dendritic BDNF synthesis. Specifically RNAi knockdown of eEF2K reduces dendritic spine stabilit...

A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and...

Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by det...

The series of international conferences on nerve growth factor (NGF) and related molecules arose from a meeting held in 1986, to mark Rita Levi-Montalcini’s 77th birthday, and in recognition of the fact that her discovery of NGF opened up the field of trophic factors. One of the best characterized families of such trophic factors is the NGF family of neurotrophins, which in mammals also include...

Experience plays a crucial role in the development of the nervous system by promoting the maturation, and elimination of synapses. We have found that synaptic stimulation by promoting calcium influx into neurons regulates a complex gene program that controls aspects of synapse development. We have identified a signaling network that conveys the calcium signal from the site of entry to the nucle...

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects ...

The interactions between a prior program of regular exercise and the development of experimental autoimmune encephalomyelitis (EAE)-mediated responses were evaluated. In the exercised EAE mice, although there was no effect on infiltrated cells, the cytokine and derived neurotrophic factor (BDNF) levels were altered, and the clinical score was attenuated. Although, the cytokine levels were decre...

The K-Cl cotransporter KCC2 plays a crucial role in the functional development of GABA(A)-mediated responses rendering GABA hyperpolarizing in adult neurons. We have previously shown that BDNF upregulates KCC2 in immature neurons through the transcription factor Egr4. The effect of BDNF on Egr4 and KCC2 was shown to be dependent on the activation of ERK1/2. Here we demonstrate that the trophic ...

BDNF has pleiotropic effects on neuronal development and synaptic plasticity that underlie circuit formation and cognitive function. Recent breakthroughs reveal that neuronal activity regulates BDNF cell biology, including Bdnf transcription, dendritic targeting and trafficking of BDNF mRNA and protein, and secretion and extracellular conversion of proBDNF to mature BDNF. Defects in these mecha...

BDNF is an important marker of neuronal plasticity. It has also been associated with pain processing. Increased BDNF levels are observed in chronic pain syndromes. In order to understand the role of BDNF associated with other factors such as gender on experimental pain we aimed to determine whether experimental heat or pressure pain threshold is correlated with brain derived neurotrophic factor...