An earlier microarray analysis utilizing neuroblastoma SH-SY5Y documented that lithium elicited more than 900 statistically considerable gene expression modifications and, in specific, the Six1 gene mediated lithium protection against staurosporine-induced apoptosis by blockade of caspase-3 activation.68 A recent microarray evaluation discovered that lithium differentially regulated the expression of more than 50 genes including fundamental transcription factors, transcription activators, cell signaling proteins, cell adhesion proteins, oncogenes and tumor suppressors, intracellular transducers, survival and death genes, and cyclins.69 In yet another recent microarray study using rat cerebellar granule cells and SH-SY5Y cells, lithium and valproate mixture was discovered to be protective against glutamate excitotoxicity and also the neuroprotection was connected with downregulation of a prominent microRNA, miR-34a.70 Neurotrophins and Development Things. The effects of lithium on neurotrophin expression are several, and may perhaps rely on brain state, area, and species (for a review, see ref 16) Depression has been reported to minimize brain levels of BDNF,71,72 and lithium is identified to raise BDNF levels in the brain.72-75 Lithium and valproate both selectively activated BDNF promoter IV of primary neurons76 and elevated BDNF levels in rat hippocampal, frontal, and temporal cortices,77,78 but not the mouse thalamus.79 Acute and long-term lithium remedy were both located to increase the BDNF receptor TrkB in the mouse anterior cingulate but not inside the hippocampus, although acute lithium substantially decreased CREB phosphorylation, a crucial intracellular target of TrkBmediated signaling.80 This lower in CREB phosphorylation is in contrast to an elevated phospho-CREB level reported previously in an in vivo and in vitro study following lithium treatment,44 as well as the discrepancy may stem from differences in the experimental circumstances for example the duration of drug remedy and brain regions examined. These above-mentioned findings assistance the suggestion that BDNF release and receptor activation can be elevated by lithium. One study even located that particular BDNF polymorphisms can predict response to lithium in individuals with bipolar depression,81 in addition to a clinical trial in individuals with Alzheimer's illness located that lithium increased serum BDNF levels, and that this was accompanied by reductions in cognitive impairment. 82 Interestingly, lowered levels of BDNF happen to be reported in BD sufferers,83 and lithium therapy has also been found to restore and also.<br />

    Humphrey Bang
    By Humphrey Bang
    Pending Moderator Review