| 1 | Brain Nerve 2010 Dec 62: 1315-22 |
|---|---|
| PMID | 21139184 |
| Title | [Molecular mechanism and mental function of postnatal neurogenesis]. |
| Abstract | Postnatal neurogenesis has been observed in two brain regions: the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, among vertebrates including human. Accumulating evidence has indicated the molecular mechanisms commonly underlying embryonic and adult neurogenesis. Genetic factors essential for neural development, i.e., Pax6, Fabp7, SOX2, Wnt3, Notch1, etc., are also expressed in adult neurogenic regions. Adult neurogenesis, however, is distinct from embryonic neurogenesis in that the former is activity dependent; environmental stimulation modulates the entire processes of adult neurogenesis. In the hippocampus, physical exercise and cognitive stimuli robustly increase the proliferation of precursor cells, whereas physical/psychosocial stress decreases the proliferation of newborn neurons. Thus, adult neurogenesis is intriguingly regulated by several genetic and environmental factors. Reduction in hippocampal neurogenesis during the infantile and adult stages has been observed in some animal models of mental illness such as schizophrenia and major depression, implicating that postnatal neurogenesis may contribute to a part of the symptoms of mental illness. In this review, we describe the molecular mechanisms and functional significance of postnatal neurogenesis. |
| SCZ Keywords | schizophrenia |
| 2 | Proc. Natl. Acad. Sci. U.S.A. 2013 Nov 110: 19472-7 |
| PMID | 24218577 |
| Title | Human-specific endogenous retroviral insert serves as an enhancer for the schizophrenia-linked gene PRODH. |
| Abstract | Using a systematic, whole-genome analysis of enhancer activity of human-specific endogenous retroviral inserts (hsERVs), we identified an element, hsERVPRODH, that acts as a tissue-specific enhancer for the PRODH gene, which is required for proper CNS functioning. PRODH is one of the candidate genes for susceptibility to schizophrenia and other neurological disorders. It codes for a proline dehydrogenase enzyme, which catalyses the first step of proline catabolism and most likely is involved in neuromediator synthesis in the CNS. We investigated the mechanisms that regulate hsERVPRODH enhancer activity. We showed that the hsERVPRODH enhancer and the internal CpG island of PRODH synergistically activate its promoter. The enhancer activity of hsERVPRODH is regulated by methylation, and in an undermethylated state it can up-regulate PRODH expression in the hippocampus. The mechanism of hsERVPRODH enhancer activity involves the binding of the transcription factor SOX2, whch is preferentially expressed in hippocampus. We propose that the interaction of hsERVPRODH and PRODH may have contributed to human CNS evolution. |
| SCZ Keywords | schizophrenia |
| 3 | Psychiatry Investig 2015 Oct 12: 532-7 |
| PMID | 26508965 |
| Title | Increases in iPS Transcription Factor (Oct4, Sox2, c-Myc, and Klf4) Gene Expression after Modified Electroconvulsive Therapy. |
| Abstract | Electroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, SOX2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka's four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. We compared the peripheral blood gene expression of the four iPS genes (Oct4, SOX2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. Both assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for SOX2; and at the 3rd, 6th and 10th mECT for c-Myc. These significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT. |
| SCZ Keywords | schizophrenia |