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5 - 5 - 44. Major depression. Additional Antidepressant Mechanisms (11-12)

5 - 5 - 44. Major depression. Additional Antidepressant Mechanisms (11-12)

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This lecture continues our discussion of antidepressant drugs and how they might be acting. The first topic is neurogenesis. In adult rodents, and in adult monkeys, and perhaps in adult humans, it's not yet certain, new neurons form continuously from progenitor cells, a type of restricted stem cell located near the hippocampus, in a place called the subgranular zone. These neurons differentiate, they become incorporated into neuronal circuits in a region of the hippocampus called the dentate gyrus. so they become granule cells in the granule cell layer and extend their dendrites into the molecular layer, ML. It is thought that these newly born migrated neurons, maybe more active and may have special characteristics that the mature neurons don't. And so the thinking is that perhaps, these new neurons are more important for antidepressant actions than are the remaining adult neurons. Now it is very clear that some antidepressants do result in additional hippocampal neurogenesis. Not clear whether this happens in people, but clear in mice. And so, the question becomes how do antidepressants produce neurogenesis? The possibility is that the antidepressants result in the release of growth factors, of the, the sort that we have already discussed. And that these then prroduce new neurogenesis that the newly derived neurons become incorporated into hippocampal circuitry. And this then, via the diagrams that we saw in miniLecture 42 might affect the ventral brain, the amygdala, the nucleus accumbens, as well as the prefrontal cortex. And might in turn, be influenced by other brain regions including the HPA axis. So, whether and to what extent neurogenesis is involved in antidepressant action remains to be seen over the next few years. I want to remind you also that some modern antidepressants are not simply serotonin reuptake inhibitors, but mixed serotonin and norepinephrine reuptake inhibitors. And so, many experts ask, how does blockage of noradrenaline reuptake, relieve depression via the presumed outside-in mechanis ms?
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