In a pretty recent rat model study, mRNA microarray tactic and quantitative genuine time PCR (q-PCR) were utilized to demonstrate for the very first time that FGF-21 is expressed in main brain neurons, and that lithium increases FGF-21 mRNA and protein expression levels through GSK-3 inhibition.124 That study also located that FGF-21 is selectively and synergistically elevated by cotreatment with lithium andReviewvalproate via enhanced lithium-induced GSK-3 inhibition and Akt-1 activation, also as valproate-induced histone deacetylase (HDAC) inhibition.124 In this proposed complex pathway, the lithium-valproate mixture induces Akt-1 to act as an upstream regulator of FGF-21 expression at the same time as a downstream mediator for FGF-21-induced neuroprotection.124 Deemed with each other, these novel results indicate that FGF-21 is an critical mediator with the protective effects of those mood stabilizers, and holds great promise as a new therapeutic target for CNS disorders, including TBI and other folks with an underlying excitotoxic element. Neurogenesis. Numerous preclinical studies have located that lithium induces neurogenesis (for any evaluation, see ref 16). In a rodent quinolinic acid-induced striatal injury model, short-term lithium exposure activated neurogenesis; the proliferating cells showed astroglial and neuronal phenotypes, suggesting that the newly formed cells were neural stem cells.125 In other research, chronic lithium therapy enhanced neurogenesis within the hippocampus in the rat dentate gyrus;126,127 however, in older rats, it enhanced long-term potentiation but not neurogenesis.128 Lithium also selectively enhanced differentiation of hippocampal neural progenitor cells both in vitro and in vivo.129 Insight into the prospective mechanisms by which lithium can induce neurogenesis has advanced considerably. It was noted that lithium could prevent stress-induced reductions in VEGF levels and this, as previously mentioned, can stimulate each neurogenesis and angiogenesis.118 In rats, chronic mild strain led to decreased hippocampal cell proliferation; this kind of anxiety could enhance GSK-3 mRNA expression and total GSK3 protein expression.130 Lithium could block the unfavorable effects of chronic-mild pressure, suggesting that GSK-3 inhibition is involved in preventing the adverse effects of stress on behavior and cellular processes.

    Humphrey Bang
    By Humphrey Bang
    Pending Moderator Review