Published studies have primarily focused on understanding bipolar disorder pathology, but initial work is also being done to use iPS technology for drug discovery. In general, iPS and related cells can be used for studies of disease pathology, drug discovery, or stem cell therapy. Others still have utilized olfactory epithelium tissue as a source of neural-like cells that do not need reprogramming. However, others have been able to transdifferentiate fibroblasts directly to neurons. So far, most work has used the prototypical iPS cells. We selectively reviewed the literature related to understanding bipolar disorder based on using neurons derived from iPS cells. A number of groups are starting to apply iPS technology to the study of bipolar disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons.īipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. Our findings highlight the critical role of RP58 in multipolar-to- bipolar transition via suppression of the Ngn2-Rnd2 pathway in the developing cerebral cortex. Finally, we found that RP58 represses Ngn2 transcription to regulate the Ngn2-Rnd2 pathway Ngn2 knockdown rescued migration defects of the RP58−/− neurons. Cre-mediated deletion of RP58 using in utero electroporation in RP58flox/flox mice revealed that RP58 functions in cell-autonomous multipolar-to- bipolar transition, independent of cell-cycle exit. RP58−/− neurons exhibited severe defects in the formation of leading processes and never shifted to the locomotion mode. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to- bipolar transition. However, the molecular mechanisms underlying neuronal migration remain largely unknown. RP58 Regulates the Multipolar- Bipolar Transition of Newborn Neurons in the Developing Cerebral Cortexĭirectory of Open Access Journals (Sweden)įull Text Available Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is an increased rate of neuronal birth and death during this development period. Neuronal migration, apoptosis and bipolar disorder.īipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment.
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