Sleep Deprivation Inhibits Expression of NADPH-d and NOS while Activating Microglia and Astroglia in the Rat Hippocampus

Abstract

This study investigated the expression of nitric oxide (NO)-synthesizing enzymes and the glial reaction in the rat hippocampal formation following sleep deprivation for 5 days. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity was markedly reduced in the hippocampal CA1, CA2 and CA3 sectors as well as in the dentate gyrus, suggesting a suppression of NO production in these areas. Microglial cells were hypertrophic and showed an up-regulation of complement type 3 receptors as determined by antibody OX-42. However, expression of major histocompatibility complex class I and II antigens, and antigen of monocyte/macrophage lineage marked by OX-18, OX-6 and ED1, respectively, was undetected. Astrocytes also displayed hypertrophied processes with enhanced glial fibrillary acidic protein (GFAP) immunoreactivity. Western blots of hippocampal tissues corroborated the above-mentioned morphological findings in that expression of NO-synthase (NOS) was decreased while that of OX-42 and GFAP was increased in the sleep-deprived rats. Since NO is thought to be involved in memory consolidation processes in the hippocampus during sleep, the inhibition of NADPH-d and NOS reactivities may account for the memory decline after long-term sleep deprivation. The concomitant reactions in microglia and astrocytes suggest the involvement of these cells in the deleterious effect of prolonged sleep deprivation.

Chronic sleep restriction during development can lead to long-lasting behavioral effects

“…Microglia are part of the response to PGE2 in masculinized brains, and are at a higher density and are more activated in male rats [30]. They are also activated by sleep deprivation [31] and activated microglia are a feature commonly associated with autism [32, 33]. Perhaps male mice, with already higher numbers of activated microglia, are less able to handle the effects of further activation of microglia in response to sleep restriction.…”

Resolvins AT-D1 and E1 differentially impact functional outcome, post-traumatic sleep, and microglial activation following diffuse brain injury in the mouse

“…It remains likely that increased post-traumatic sleep of RvE1-treated mice, possibly a protective response, may promote resolution of inflammation as indicated by fewer activated rod microglia, albeit without functional benefit. Since sleep disruption results in microglial activation 63 without worsening functional outcome after diffuse TBI in mice 35 , the effect of disrupting post-traumatic sleep in RvE1 treated mice would be intriguing.…”

Can sleep apnea cause Alzheimer's disease?

“…The important role of astrocytes in regulating sleep pressure is consistent with their function in glycogen storage and metabolic coupling (Petit et al, 2010). Reactive astrogliosis is seen in the brainstem of patients with sudden infant death syndrome (Sawaguchi et al, 2002(Sawaguchi et al, , 2003, and in the hippocampus of rats 5 days after sleep deprivation, when nitric oxide synthase and nicotinamide adenine dinucleotide phosphatediaphorase reactivity is inhibited (Hsu et al, 2003). Thus, an association of OSA with reactive astrogliosis is not surprising, and it is supported by a specific increase of serum S100␤ in OSA patients.…”