Mechanisms Of Retinoic Acid On The Induction Of Differentiation Of Neural Stem Cells From Newborn Rat Striatum

BACKGROUNDNeural stem cells (NSCs) are undifferentiated cells with the capacity for unlimited or prolonged self-renewal and the ability to differentiate and form the three terminal functional cells of nervous system, which are neurons, astrocytes and oligodendrocytes. NSCs are one of the most attractive cells for an application of neural transplantation or drug discovery for neurodegenerative diseases such as Parkinson's disease, Huntington's disease, nerve injury, stroke and so on. Therefore, many studied have been performed to investigate the mechanisms involved in the proliferation and differentiation of NSCs. The differentiation of NSCs is affected by internal factors (gene controls) and external factors (sunounding environment of cells).Vitamin A is a micronutrient with an unusually wide biological scope of action including morph genesis, vision, immune function, reproduction, neuronal development, and maintenance of differentiate function. For many years, its specific mechanisms of action, beyond those identified for vision, remained elusive. Recent identification of multiple nuclear receptors for the vitamin A metabolite retinoic acid(RA) has allowed a greater understanding of its myriad of cellular effects and its ability to modulate a broad spectrum of events. RA is known to induce neural tissue-type differentiation in various preparations including embryonic carcinoma cell lines and embryonic stem cells. RA is also shown to induce neuron formation in NSCs. In this work, we studied on the effects and mechanisms of RA on the proliferation and differentiation of newborn rat'striatal NSCs.During brain development, RA signals key events leading to the cessation of cell proliferation and terminal differentiation and consequently can be considered a neurotrophin. RA has been shown to regulate the expression of genes involved on cell proliferation and differentiation. However, the molecular mechanisms of RA action remain an unsolved problem. The data indicates that the action of RA in the control of gene expression is mediated by its receptors [Retinoic acid receptors (RARs) and /or RA receptors (RAR)] within the nucleus. RA binds to cellular RA-binding protein (CRABP) in the cytosol transport RA to nuclear and convert to RA, which then binds to its receptors. The ligand receptor complex modulates gene expression by binding as homo- or heterodimers to specific DNA sequences known as RA response elements (RARE) located in the promoter region of the target gene. To further define the function of RA in the molecular mechanisms of induction of neuronal different ion, it is necessary to identify the relative target gene of RA.One of the early events in neuronal differentiation involves alternations in cell-cycle protein expression and exit from cell cycles. The cyclin-dependent kinases are key players in cell proliferation and differentiation. RA may induce the neural differentiation of NSCs through regulation the expression of cyclin-dependent kinases. Recent studied have showed that the POU transcription factors regulate the differentiation of NSCs in vertebrate. Brn-4 mediated, at least in part, the action of epigenetic signals that induce striatum neuron-precursor differentiation. Both the...