Glutamate treatment mimics LTP- and LTD-like biochemical activity in viable synaptosome preparation.

Long-term potentiation (LTP) and long-term depression (LTD) are considered to be the cellular mechanisms behind the increase or decrease of synaptic strength respectively. Electrophysiologically induced LTP/LTD is associated with the activation of glutamate receptors in the synaptic terminals resulting in the initiation of biochemical processes in the postsynaptic terminals and thus propagation of synaptic activity. Isolated nerve endings i.

Thyroid Hormone and Astrocyte Differentiation.

Thyroid hormones (THs) have important contributions to the development of the mammalian brain, targeting its actions on both neurons and glial cells. Astrocytes, which constitute about half of the glial cells, characteristically undergo dramatic changes in their morphology during development and such changes become necessary for the proper development of the brain. Interestingly, a large number of studies have suggested that THs play a profound role in such morphological maturation of the astrocytes.

Essential role of docosahexaenoic acid towards development of a smarter brain.

Evolution of the high order brain function in humans can be attributed to intake of poly unsaturated fatty acids (PUFAs) of which the ω-3 fatty acid, docosahexaenoic acid (DHA) has special significance. DHA is abundantly present in the human brain and is an essential requirement in every step of brain development like neural cell proliferation, migration, differentiation, synaptogenesis etc. The multiple double bonds and unique structure allow DHA to impart special membrane characteristics for effective cell signaling.

BDNF local translation in viable synaptosomes: implication in spine maturation.

The neurotrophic factor, BDNF, is encoded by two transcripts, one short and another long 3' untranslated region containing mRNA. Long BDNF mRNA was found to transport to the dendrites; however report about its translation or regulation of translation in the dendrite remains unknown. Using synaptosomes, to isolate from the nucleus and other subcellular fractions involved in translation, we demonstrate that depolarization by KCl or excitation by glutamate can induce translation of BDNF.

Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin.

Mutations in the Bdnf gene, which produces transcripts with either short or long 3' untranslated regions (3' UTRs), cause human obesity; however, the precise role of brain-derived neurotrophic factor (BDNF) in the regulation of energy balance is unknown. Here we show the relationship between Bdnf mRNA with a long 3' UTR (long 3' UTR Bdnf mRNA), leptin, neuronal activation and body weight. We found that long 3' UTR Bdnf mRNA was enriched in the dendrites of hypothalamic neurons and that insulin and leptin could stimulate its translation in dendrites.

Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons.

The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with either short or long 3' untranslated regions (3' UTRs). The physiological significance of the two forms of mRNAs encoding the same protein is unknown. Here, we show that the short and long 3' UTR BDNF mRNAs are involved in different cellular functions.

Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice.

Huntington's disease (HD), a dominantly inherited neurodegenerative disorder characterized by relatively selective degeneration of striatal neurons, is caused by an expanded polyglutamine tract of the huntingtin (htt) protein. The htt mutation reduces levels of brain-derived neurotrophic factor (BDNF) in the striatum, likely by inhibiting cortical BDNF gene expression and anterograde transport of BDNF from cortex to striatum. However, roles of the BDNF reduction in HD pathogenesis have not been established conclusively.

Thyroid hormone-induced morphological differentiation and maturation of astrocytes involves activation of protein kinase A and ERK signalling pathway.

Thyroid hormone (TH) has a profound effect on astrocyte differentiation and maturation. Astrocytes cultured under TH-deficient conditions fail to transform from flat polygonal morphology to mature, process-bearing, stellate cells. Supplementation of physiological concentrations of TH initiate gradual transformation of the cells and the process takes approximately 48 h to complete.

Delayed but sustained induction of mitogen-activated protein kinase activity is associated with beta-adrenergic receptor-mediated morphological differentiation of astrocytes.

Astroglial beta-adrenergic receptors (beta-ARs) are functionally linked to regulate cellular morphology. In primary cultures, the beta-AR agonist isoproterenol (ISP) can transform flat polygonal astrocytes into process-bearing, mature stellate cells by 48 h, an effect that can be blocked by the beta-AR antagonist, propranolol. ISP induced immediate activation of protein kinase A (PKA) which persisted up to 2 h, with no visible change in cell morphology.

Role of protein-tyrosine phosphatases on beta-adrenergic receptor mediated morphological differentiation of astrocytes.

A role of protein-tyrosine phosphatases in isoproterenol induced differentiation of cultured astrocytes was investigated. Unlike serine/threonine phosphatase inhibitors, the tyrosine phosphatase inhibitor, sodium orthovanadate effectively blocked transformation of the polygonal astrocytes to process bearing stellate cells on exposure to isoproterenol for 2 days. Isoproterenol caused a stimulation of c-AMP dependent protein kinase activity in the cells only at the initial stages (45 min) and at 12 and 24 h, there was a decline in the level of phospho-tyrosinated proteins which could be antagonised by the protein kinase A inhibitor, H89.