Neurotrophins and Depression



         An interesting find in the Santarelli paper was that the effects of imipramine administration on 5HTA-KO mice still had an effect while fluoxetine did not ( This is intriguing as there are many explanations that are possible for this phenomena. The first is that the nature of these two antidepressant drugs is different entirely. Flueoxetine is an SSRI, causing a block of re-uptake of serotonin alone, while the TCA imipramine causes an increase in not only blocking re-uptake of serotonin, but norepinephrine as well, suggesting that perhaps the increase in cell proliferation arising in KO mice with imipramine administration is coming from the activation of Norepinephrine receptors. Another explanation draws support from the fact that imipramine causes increase in the acetylation pattern at the BDNF promoter, possibly causing a neurotrophic factor induced neurogenic response, as imipramine has been shown to increase level of BDNF.

         Another interesting find in the Bessa paper was that there was a difference in effects of irradiation on two different regions of the hippocampus. The SVZ showed a robust neurogenic response against irradiation. this is perhaps explained by the fact that astrocytes in the SVZ stimulate neurogenesis there (Lim, Daniel A, 1999).  Perhaps there is a greater density of astrocytes in the SVZ than the SGZ explaining the discrepancy. This might change our research focus on perhaps isolating a host of different factors that are secreted by astrocytes that stimulate neurogenesis. Perhaps most of the neurogenesis in the brain is first signaled by astrocytes as well. Further research into effects of knocking out astrocytes and supporting glial fates in the hippocampus to assess rates of neurogenesis  and consequently depressed phenotypes would prove useful and revealing.
     

References:

Lim, Daniel A, and Arturo Alvarez-Buylla. “Interaction between Astrocytes and Adult Sub-Ventricular Zone Precursors Stimulates Neurogenesis.” Proceedings of the National Academy of Sciences of the United States of America, vol. 13, no. 7526, 22 June 1999, pp. 7526–7531.

 Santarelli, Luca. “Requirement of Hippocampal Neurogenesis for the Behavioral Effect of Anti-Depressants.” Science, vol. 301, no. 805, 8 Aug. 2003, pp. 805–809.

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