Neurogenesis and the Effect of Antidepressants

To study the functional implication of such observations, Santarelli et al. (2003) aimed at determining if an increase in neurogenesis is required for the effect of antidepressants. X-ray irradiation of the hippocampal area in adult rats causes long-term reduction in cell proliferation in the DG (Tada et al., 2000). Hippocampal x-ray irradiation, but not irradiation of other brain areas - like the SVZ or the cerebellar region - prevented the neurogenic effect 

There are, however, controversies and debates over the involvement of the hippocampus and adult neurogenesis in the etiology of depression. Among them, i) a link between 

All these data involved the hippocampus, a structure traditionally involved in learning and memory, and adult neurogenesis in depression and anxiety disorders (Thomas and Peterson, 2003). Antidepressant treatments may increase neural plasticity and adult neurogenesis, especially in the hippocampus. However, the neurogenic theory of depression remains the source of debate and controversy, and requires further study (Feldmann et al., 

More data and evidence are needed to confirm the involvement of adult neurogenesis in depression. 

Reproduced from Taupin P. Neurogenesis and the Effects of Antidepressants. Drug Target Insights (2006) 1 13-7, with permission from Libertas Academia. 

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Eisch, Ncstler, Duman, 2000 Santarclli et al., 2003) has demonstrated that antidepressant treatment increases neurogenesis, or new cell growth, in the hippocampus. This neurogenesis may block or reverse the effects of depression on hippocampal neurons. Further, the new cell growth appears to take several weeks to occur, and this may account for the fact that antidepressant medications typically take several weeks to exert their action. The findings suggest that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the atrophy and loss of hippocampal neurons associated with depression. 

Another source of evidence supporting the neurotrophic hypothesis of depression comes from studies of the direct effects of BDNF on emotional regulation. Direct infusion of BDNF into the midbrain, hippocampus, and lateral ventricles of rodents has an antidepressant-like effect in animal models. Moreover, all known classes of antidepressants are associated with an increase in BDNF levels in animal models with chronic (but not acute) administration. This increase in BDNF levels is consistently associated with increased neurogenesis in the hippocampus in these animal models. Other interventions thought to be effective in the treatment of major depression, including electroconvulsive therapy, also appear to robustly stimulate BDNF levels and hippocampus neurogenesis in animal models. 

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