Although SSRI treatment produces robust increases in extracellular 5-HT, there is evidence that SSRI administration can actually deplete brain stores of 5-HT and of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) [64], [69] [77], as would be predicted if 5-HT synthesis were suppressed and serotonergic neurons were unable to effectively recapture released 5-HT.
15 CSD more specifically, repolarization of neuronal membrane potentials markedly increases energy metabolism 7– 9, 13 and depletes brain glucose.
It was also reported that 4-CAP and 4-CMA cause long-lasting depletion in the level of brain 5-HT and 5-hydroxyindole-3-acetic acid without depleting brain noradrenaline [ 21, 22].
In a brain tumor model, inhibiting the Notch pathway indeed depleted CD133+ brain cancer stem cells and blocked tumor initiation [44], consistent with our findings in pancreatic cancer model.
Weeks later, both dopamine and serotonin were depleted in brain tissue samples, and neurons that rely on these chemicals had damage to their axons, projections that send messages to other neurons.
Five miRNAs are specifically depleted in brain, liver or heart.
Previous reports indicated that phosphocreatine stores are quickly depleted upon brain activation, while ATP concentrations remain constant.
In one animal, a colony-stimulating factor 1 receptor kinase inhibitor, previously shown to deplete brain microglia, reduced [11C]PBR28 V T in brain by 46±3%3% from baseline, which recovered after 12 days to 7±5%5% from baseline.
The first mechanism clash with animal evidences showing that mCPP and fenfluramine do not deplete brain 5-HT [80], and that RTD which diminished brain 5-HT synthesis does not provoke migraine attack [25, 89].
