Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the subependymal layer (SEL) adjacent to the caudate nucleus in the human brain in response to neurodegeneration of the caudate nucleus in Huntington's disease (HD). Postmortem control and HD human brain tissue were examined by using the cell cycle marker proliferating cell nuclear antigen (PCNA), the neuronal marker III-tubulin, and the glial cell marker glial fibrillary acidic protein (GFAP). We observed a significant increase in cell proliferation in the SEL in HD compared with control brains. Within the HD group, the degree of cell proliferation increased with pathological severity and increasing CAG repeats in the HD gene. Most importantly, PCNA ؉ cells were shown to coexpress III-tubulin or GFAP, demonstrating the generation of neurons and glial cells in the SEL of the diseased human brain. Our results provide evidence of increased progenitor cell proliferation and neurogenesis in the diseased adult human brain and further indicate the regenerative potential of the human brain.A particularly exciting development in the treatment of neurodegenerative diseases is the suggestion from both animal and human studies that transplantation of embryonic neurons or stem cells offer a potential treatment strategy for neurodegenerative disorders such as Parkinson's disease, Huntington's disease (HD), and Alzheimer's disease (1, 2). Although in recent years the transplantation of embryonic cells into the diseased human brain has emerged from the realm of the theoretical to that of the practical, it is associated with ethical, technical, and immunological problems (2). Thus, the demonstration of endogenous stem͞progenitor cells in the hippocampus and the subependymal layer (SEL) of the basal ganglia in the adult mammalian brain has raised the exciting possibility that these undifferentiated cells may be able to generate neurons for cell replacement in neurodegenerative diseases such as HD. Indeed, neural stem cells in the rodent brain SEL adjacent to the caudate nucleus have recently been shown to proliferate and differentiate into neurons (3-5), suggesting they may provide a source of replacement neurons. In this regard it is especially interesting that recent studies (6) on the normal adult human brain have shown evidence of neurogenesis in the hippocampus, but no previous study has yet shown neurogenesis in the SEL of the normal or diseased human brain. Here, we have examined whether progenitor cell proliferation and neurogenesis occur in the SEL adjacent to the caudate nucleus in response to cell death in the caudate nucleus of the adult human HD brain. The results demonstrate increased progenitor cell proliferation and neurogenesis in the SEL of the HD brains indicating that the diseased human brai...
Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.
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