Neurons were once thought produced only during embryogenesis and soon after birth (perinatal). It is now accepted that neurogenesis persists in the adult CNS, and multipotent precursor or stem cells are present throughout adulthood (52). In the adult rodent brain, neurogenic stem cells are concentrated in the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal gyrus. There is evidence that neural stem cells may be a specific type of astrocytes residing within these regions (53, 54). There is a close association of neurogenesis with the hippocampal function of learning and memory, and newly generated neurons in the adult may participate in the formation of a hippocampaldependent memory (55, 56).
Recent studies suggest that inhibition of neurogenesis may contribute to the neurocognitive impairment after cranial XRT (9, 13, 57). In rat brain after a single XRT dose of 10 Gy, ablation of hippocampal neurogenesis occurs and neural precursors, instead, differentiate into glia cells. Transplants of non-irradiated neural precursor cells also fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by disruption of the microvascular angiogenesis associated with neurogenesis and an increase in the number and activation status of microglia (58), indicating that stem-cell differentiation is regulated by signals from the microenvironment in which these cells reside (54). Thus, in addition to clonogenic death of the neural progenitor cell population, the deficit in neurogenesis after XRT may reflect alterations in the microenvironment that regulates progenitor cell fate. These findings highlight the role of the microenvironment, in particular the presence of neuro-inflammation in mediating the damage response.
Rats with blocked neurogenesis following cranial XRT performed poorer than controls in hippocampus-dependent tasks (57). Although this finding suggests that the presence of newly generated neurons may be necessary for the intact hippocampus, it should be recognized that an enriched environment, exercise, and many other factors are associated with enhanced neurogenesis in rodents (59). The causal role of inhibition of hippocampal neurogenesis to the impairment of learning and memory function observed after XRT remains unproven.
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