Testing the role of radicals in sleep deprivation`s antidepressant effect.
By JOHN STEWART
Recent research on sleep deprivation(SD) has demonstrated in the mouse large free radical increases after two days SD, selectively in the small intestine (and large).1. This timescale closely parallels that of the quick, hard to sustain, human antidepressant effect of SD.2. Antidepressant effects of MAOIs occur only after four plus weeks of treatment. This difference can be understood, as MAOI reduction of oxidative stress.3. can reduce intracellular antioxidant levels, resulting in a progressive reduction to the point where curative gut TRPA1 activation is possible at normal radical levels.4.5. The acute SD antidepressant action is due to acutely raised supranormal radical levels overcoming gut antioxidants, resulting in TRPA1 activation, serotonin and CCK release, and vagal/trigeminal change. Falling asleep abolishes antidepressant effects of SD, and is known to rapidly reduce radical levels. A possible test for this explanation of the human sleep deprivation antidepressant effect is that it would then not be expected to occur during concurrent treatment with N-Acetyl Cysteine and deferoxamine, which abolish the "manic-like" effects of paradoxical SD in mice.6.
.1.Cell.2020.181(6);1307-1328.
.2.Journal of Clinical Psychiatry.2017.78(8).e1020-e1034.
.3.Chemico-Biological Interactions.2019.304.139-147.
.4.Neurology,Psychiatry and Brain Research.5(4):181,8(4):185,10(4):149.
.5.Journal of Brief Ideas. "Oxidative stress, MAOIs and OCD".
.6.J.Psychiatr.Res.2015.65:71-9.
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