Browsing by keyword "neurogenesis"
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Adult neurogenesis and its promise as a hope for brain repairAfter the pioneer report by Joseph Altman of adult neurogenesis (AN) in mammals in 1962, the phenomenon of AN was “rediscovered” some 20 years later, first in songbirds and then in mammals. Since the 1990s, interest in AN was fueled by the hope that it could lead to the treatment of neurological deficits by grafting these neurons or their progenitors into brain areas affected by disease or injury. Unfortunately, after 20 years of intense research efforts there is no clear indication that AN can be harnessed for the repair of brain circuits. We argue that the exuberant optimism regarding the potential application of AN for brain repair was misguided by the belief that neurons and their precursors had extensive developmental plasticity. Many of the experiments investigating the potential of AN for brain repair were inspired by the idea that neuronal precursors would be able to adapt, and easily change their developmental fate to replace the lost neurons. However, research during the last 20 years has shown that, in most cases, the fate of neurons is strongly determined and that it rarely changes. Understanding the mechanisms that control neural cell fate may allow for the engineering of adult stem cells so that they can give rise to neurons with properties appropriate for the host circuit to be repaired. The lack of phenotypic flexibility of neuronal progenitors may eventually prove to be advantageous, as this may provide a high degree of predictability (and safety) in the properties of reprogrammed cells. We suggest that AN is still a useful model to understand how neurons integrate into adult brain circuits, and that brain repair will require a thorough understanding of the genetic programs that control neuronal fate and neuronal migration.
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Ephrinb3 modulates hippocampal neurogenesis and the reelin signaling pathway in a pilocarpineinduced model of epilepsyEphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis. The data revealed that the mRNA and protein expression levels of ephrinB3 in the hippocampus decreased during the spontaneous seizure period. Of note, the expression of reelin and its downstream phosphorylation disabled 1 (pDab1) were also notably decreased during the spontaneous seizure period, which showed similar dynamic changes as in the expression of ephrinB3. In addition, it was found that the number of DCXlabeled neuronal progenitor cells was increased in the hippocampus following pilocarpineinduced SE. To further clarify the role of ephrinB3 in neurogenesis and the reelin pathway in epilepsy, an exogenous ephrinB3 clustering stimulator, EphB3Fc, was infused into the bilateral hippocampus of the rats postSE. Following EphB3Fc injection, it was found that the expression levels of reelin and pDab1 were significantly increased in the epileptic rats following EphB3Fc injection. The number of DCXlabeled neuronal progenitor cells was reduced in the hippocampus of the epileptic rats. Furthermore, the intensity and frequency of spontaneous recurrent seizures and electroencephalographic seizures were attenuated in the epileptic rats postinjection. These results demonstrated the critical role of ephrinB3 in regulation of the reelin pathway and hippocampal neurogenesis in epilepsy, providing experimental evidence that ephrinB3 functions as a potential protective factor in epilepsy, at least in animals.
