| The dogma that the brains of adult mammals do not generate new nerve cells have been challenged by recent data showing that new cells are generated throughout the central nervous system (CNS) well into adulthood in all mammals, including humans. Neurogenesis in the adult brain is convincingly demonstrated within the subventricular zone of the forebrain (SVZ) and the subgranular layer of hippocampal dentate gyrus (DG). There is extensive evidence showing that new neurons are added to the dentate gyrus of adults in many species of vertebrates. Newly generated neurons in the adult hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granulecells. Hippocampus is an important region of learning and memory in the brain, so neurogenesis in the hippocampus plays a significant role in brain repair after damage.Neurogenesis is a dynamic process that is regulated by environmental, endocrine, and pharmacological stimuli. Ischemia, hypoxia and insults can damage brain issue occurring by neurogenesis. Global or focal forebrain ischemia causes selective degeneration of hippocampal CA1 pyramidal neurons, and it also increases the birth of dentate progenitor cells in the rodent SGZ. Middle artery occlusion (MCAO) stimulating focal brain ischemia can induce neurogenesis in SGZ of hippocampal. After cerebral ischemia, newly born neurons are directed towards the sites of damaged striatum and cerebral cortex, where they participate in brain repair and functional recorvery. The molecular events underlying the proliferation of progenitors and the migration of newborn neurons into injured tissue after cerebral ischemia insults are only partly understood. Glutamate may be involved in neurogenesis in dentate gyrus after brain ischemia in rats. The molecular mechanism is thought to be concerned with calcium ion. Calcium influx depends mostly on NMDA-Receptors and L-type calcium channels. It exerts in many processes of pathology and physiology. L-typevoltage-gated calcium channels (L-VGCCs) consist with alC (D) subunit and secondary subunit. The C-terminal location of alC (D) subunit contains many functional domains, and it can interact with Src family protein tyrosine kinases (SrcPTKs), cAMP-dependent protein kinases, etc. With that, they regulate calcium stabilization, gene expression, hormone incretion and other activities. Just as the signal system inside the cells, Ca2+ influx induced by NMDA-Receptors and L-type calcium channels may have same sense. So, we suppose that L-type calcium channels can regulate neurogenesis.NO is an important neurotransmitter which can regulate cell survival and synaptic plastics, etc. Recent studies suggest that NO also participates in neurogenesis in hippocampus. NO is produced from arginine by NO synthase (NOS). Three distinct members of the NOS family in mammalian cells have been identified: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Both nNOS and eNOS are constitutively expressed in many tissues, while iNOS is not usually expressed in the CNS in normal. But iNOS can be induced by inflammation. The activities of nNOS and eNOS are regulated by Ca2+, while iNOS is Ca2+-independent. But it has been proved that Ca2+ can regulate iNOS expression.Focal cerebral ischemia increases the number of new neurons occuring by aboundance production of NO. Administration of DETA/NONOate to rats subjected to MCAO significantly increases cell proliferation and migration in the SVZ and DG, and these rats exhibit significant improvements of neurological outcome during recovery from ischemic stroke. The results of our lab showed that the iNOS inhibtor AG can inhibit ischemia-induced neurogenesis in the dentate gyrus. The number of BrdU+cells in the dentate gyrus in iNOS-/- mice after the ischemic insult is much Jess than in iNOS+/+ mice, demonstrating expression of iNOS is necessary for ischemia-stimulated cell birth in the dentate gyrus. So we suggest that L-typ...
|
PDF Full Text Request