Transcriptional activation induced by neuronal activity and growth factors is a pivotal control mechanism of neuronal development ; this process is specifically regulated by multiple mechanisms including post-translational modifications such as phosphorylation, ubiquitination, and SUMOylation. Another level of regulation lies in the control of the subcellular localization of transcriptional regulator through intracellular trafficking. Indeed, our previous findings demonstrate that the growth factor neuregulin stimulates the nuclear accumulation of p35. Our unpublished data also suggest that depolarization induces the translocation of p35 and NIF-1 from the cytoplasm to the nucleus in Rapamycin customer reviews cortical neurons. Thus, it is interesting to speculate that neuronal activity or growth factors are able to relay extracellular signals to the nucleus through the regulation of nucleocytoplasmic trafficking of p35 and thus its associated proteins, thereby modulating transcriptional mechanisms in neurons. The p35-mediated nucleocytoplasmic shuttling of NIF-1 is able to modulate the access of NIF-1 to the transcriptional complex and thus the regulation of gene activation and/or transcription termination. However, further studies are required to determine which signals regulate p35-mediated nuclear export. Many transcription factors that were initially found to be localized in the nucleus were subsequently shown to be expressed in the cytoplasmic regions and exert specific functions. For example, the localization of the transcription factors Stat3 and neurogenin-3 to cytoplasmic compartments is important for their functions in tumorigenesis and synaptogenesis, respectively. NIF-1 plays an important role in early neurogenesis through transcriptional regulation. However, whether the protein exerts cytoplasmic functions or has functional roles during the later stage of brain development remains to be elucidated. It is noteworthy that NIF-1 was prominently expressed in the nuclear fraction of embryonic rat brains and decreased upon postnatal development, whereas p35 increased gradually from the late stage of embryonic development to postnatal development. Thus, it is interesting to speculate that the nuclear export of NIF-1 by p35 may lead to the termination of the nuclear functions of NIF-1 and resulting in protein degradation. Taken together, the present findings reveal a newly identified NES on p35 that regulates the nucleocytoplasmic shuttling of p35. This protein trafficking mechanism may result in the redistribution of p35 and its interacting partners between the nucleus and cytoplasm, thus demonstrating a new molecular mechanism by which p35 modulates gene transcription. In the last decade, it has become clear that there is a biological link between inflammation and depression. In patients with depression, several studies have demonstrated increased expression of proinflammatory cytokines, chemokines, acute phase reactants, and adhesion molecules compared to non-depressed controls. However, there is ongoing debate on whether elevated systemic inflammation is a biological mechanism leading to depression. A few population-based studies have investigated the relationship between C-reactive protein and de novo depression. In a study including 644 women with no prior history of depression, of whom 48 women developed depression during the 5827 personyears of follow-up, CRP was found to be an independent predictor of depressive disorder, supporting an aetiological role for inflammatory activity in the pathophysiology of depression. Two larger population-based studies have investigated the direction of the depression-inflammation relationship.