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Sleep deprivation triggers inducible nitric oxide-dependent nitric oxide production in wake-active basal forebrain neurons

, , , and . J Neurosci, 30 (40): 13254-13264 (October 2010)
DOI: 10.1523/JNEUROSCI.0014-10.2010

Abstract

Sleep loss negatively impacts performance, mood, memory, and immune function, but the homeostatic factors that impel sleep after sleep loss are imperfectly understood. Pharmacological studies had implicated the basal forebrain (BF) inducible nitric oxide (NO) synthase (iNOS)-dependent NO as a key homeostatic factor, but its cellular source was obscure. To obtain direct evidence about the cellular source of iNOS-generated NO during sleep deprivation (SD), we used intracerebroventricular perfusion in rats of the cell membrane-permeable dye diaminofluorescein-2/diacetate (DAF-2/DA) that, once intracellular, bound NO and fluoresced. To circumvent the effects of neuronal NOS (nNOS), DAF-2/DA was perfused in the presence of an nNOS inhibitor. SD led to DAF-positive fluorescence only in the BF neurons, not glia. SD increased expression of iNOS, which colocalized with NO in neurons and, more specifically, in prolonged wakefulness-active neurons labeled by Fos. SD-induced iNOS expression in wakefulness-active neurons positively correlated with sleep pressure, as measured by the number of attempts to enter sleep. Importantly, SD did not induce Fos or iNOS in stress-responsive central amygdala and paraventricular hypothalamic neurons, nor did SD elevate corticosterone, suggesting that the SD protocol did not provoke iNOS expression through stress. We conclude that iNOS-produced neuronal NO is an important homeostatic factor promoting recovery sleep after SD.

Description

We all know that various chemical exposures can trigger symptoms, and many of us also have experiences with non-native EMFs. But we seldom talk about other ways to trigger symptoms in environmental illness. For example, many point out that situations of high stress can induce reactions. Others have said that intense energy exertion can do the same. Others point to temperature changes and even harsh lighting. I have observed these in myself as well, and another big one that I have observed in myself is sleep deprivation. What do all of these things have in common, including chemical and EMF exposure? They all play an active role in stimulating some aspect of the biochemical cycle of nitric oxide and peroxynitrite in the brain (usually NMDA activation). In my view, true avoidance therapy is more than just avoiding toxicant exposures. And it's more than just avoiding EMF exposures. Complete avoidance, in this sense, includes avoidance of all activities that contribute to NMDA activation. That means getting enough sleep and sleeping on a regular schedule. That means becoming intimately familiar with stress and actively employing strategies to reduce it. That means regular physical activity, but not pushing it too far. That may also mean getting plenty of healthy fats in your diet and reducing sugars and carbohydrates. And at the risk of Annie Hoppering all over you, it may also mean airy fairy stuff like developing meaningful relationships and feelings of self-worth.

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