A major goal of this study was to elucidate the rela tionship between PKA MAPK pathways and the in creased neurogenesis selleck compound we reported previously in OHSC using both immunostaining and DCX positive cell counts. As shown in Figure 7B, analysis by Western Blot revealed that concurrent chemical inhibition of PKA and MEK activation specifically attenuated the in crease in the neuroblast cell marker DCX. In accordance with the results obtained in the present study, these kinases have been reported to mediate growth factor induced neurogenesis and neuroprotection. The extracellular Inhibitors,Modulators,Libraries signal regulated kinase is activated by MEK in response to growth stimuli and much evidence exists that the ERK pathway plays a role in progenitor cell proliferation or differentiation in a number of model systems.

Inhibitors,Modulators,Libraries For example, the ERK path way is involved in neurogenesis, neurite outgrowth, and neuronal survival induced by either neurotrophic factors or pharmacological agents such as val proate or lithium and it has been proven that ERK activation promotes hippocampal neurogenesis in vivo and in vitro. Similarly, PKA regulation of transcription via CREB has been associ ated with growth factor dependent neurogenesis, cell survival, synaptic transmission and cognitive function in the nervous system. Phosphorylation of CREB and overexpression of BDNF have been implicated in the regulation of the expression of many genes and cellular processes important in brain function and the up regulation of hippocampal cell proliferation.

We have previously shown that neurogenesis after DOM insult in OHSC occurred pri marily during the first week of exposure in both the subgranular zone of the hippocampus and in the CA1 hippocampal subfield, with a decreasing tendency clearly observed over the next days. In the current study, DOM insult induced a significant long lasting increase Inhibitors,Modulators,Libraries in BDNF protein levels in OHSC that was sustained throughout the 14 day period, although in the current study we did not determine if this Inhibitors,Modulators,Libraries effect was regionally selective. BDNF is one of the most studied extrinsic fac tors that not only promotes neurogenesis, but also regu lates dendrite outgrowth, increases proximal dendrite Inhibitors,Modulators,Libraries growth and number in pyramidal neurons and promotes synaptogenesis and neuronal survival during development.

Our results suggest that BDNF in OHSC may be promoting neuro genesis as well as maturation and integration of new neurons after DOM insult, although the specific hippo campal regions at which these neurons originate, whether they in fact migrate to, or originate in, areas of transient damage, and whether they are capable selleck Idelalisib of re storing normal function to the resulting circuitry needs to be determined. Conclusions We have demonstrated that transient excitotoxic insult induced by DOM promotes sustained BDNF and TrkB overexpression in OHSC as well as increased hippocam pal neurogenesis.