Factors modulating neurogenesis may contribute to the pathophysiology of affective disorders such as major depression. Environmental stressors in animal models have been proposed to alter neurogenesis, suggesting a mechanism for this contribution. The effect of an acute psychosocial stressor on either proliferation or survival (immediate, short term, and long term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague Dawley rats. Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially relevant model. We found that exposure to an acute psychosocial stressor at the time of cell generation resulted in a decreased number of newly generated cells in the hippocampus. By using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we showed that short-term survival but not initial proliferation or immediate survival was altered in response to stress. Furthermore, we determined that stress experienced subsequent to proliferation also diminished long-term survival of cells. Thus, an acute episode of a social stress produces long-lasting effects on the incorporation of new hippocampal neurons by reducing their survival.

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Combination chemotherapy is superior to single-agent chemotherapy for treating canine lymphoma, but the effect of each drug on efficacy remains unknown. By comparing 34 dogs treated with a modified cyclophosphamide, vincristine, prednisone (COP) chemotherapy protocol and 42 dogs given asparaginase in the induction phase of the same protocol, the effect of asparaginase on the chemotherapeutic protocol was determined. Both groups were compared based on clinical response at 2 weeks and 6 weeks, and on the progression-free interval. Asparaginase did not significantly increase the likelihood of a clinical remission or prolong the initial progression-free interval in the dogs studied.

Neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells in the adult CNS. This natural generation of new cells is limited in its regenerative capabilities and also declines with age. The use of stem cells in the treatment of neurodegenerative disease may hold great potential; however, the age-related incidence of many CNS diseases coincides with reduced neurogenesis. This review concisely summarizes current knowledge related to adult neurogenesis and its alteration with aging and examines the feasibility of using stem cell and gene therapies to combat diseases of the CNS with advancing age. Keywordsaging; cell therapy; gene therapy; neurogenesis; stem cell There are few therapeutic options for restoring neurologic function following brain injury or disease at present. Thus, there is broad appeal for the idea that stem cells could be used as therapeutic intervention for age-related cognitive decline and neurodegenerative disorders as successfully as hematopoietic stem cells are used for the treatment of leukemia. The incidence of age-related neurodegenerative disorders can be expected to increase, given that the number of adults over the age of 65 years is expected to increase to 20% of the US population by the year 2050 [1]. As medical care continues to improve longevity, the achievement of successful aging will have tremendous individual and economic importance.Aging, simply the act of living longer, is a major risk factor for the development of neurodegenerative disorders as illustrated by the median onset age for diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and others [2][3][4]. Although extensive research into the etiology of such diseases has yet to define a common causal factor, this inability to identify causality is congruent with the high variability of the aging process itself. If we define 'successful aging' as those older individuals who are able to function independently with intact cognitive capacity, then 'pathological aging' runs the spectrum from dementia to culturally expected forgetfulness with individuals exhibiting highly variable functional decline over a similar lifespan. Likewise, the onset and progression of neurodegenerative disorders is quite variable.

The rate of adult neurogenesis fluctuates in response to several environmental factors. Chronic stress, which can lead to neuronal apoptosis and dendritic atrophy, certainly affects the overall rate of neurogenesis in the adult brain. Depression, which arises from several causes, including chronically stressful situations, is known to correlate with altered hippocampal morphology. But is the link between depression and neuronal regeneration merely coincidental? Recent studies indicate that ingestion of antidepressants leads to increased neurogenesis in the hippocampus. However, the hippocampus is generally thought important for learning and memory-not for "mood" state-thus, there is much more to the story that requires clarification. Also, caveats abound in the interpretation of neurogenesis in the amelioration of depression; nonetheless, these results are quite intriguing and might point to better design and prediction of new-generation antidepressants.