Microglia and the Aging Brain: Are Geriatric Microglia Linked to Poor Sleep Quality?

Abstract

Poor sleep quality and disrupted circadian behavior are a normal part of aging and include excessive daytime sleepiness, increased sleep fragmentation, and decreased total sleep time and sleep quality. Although the neuronal decline underlying the cellular mechanism of poor sleep has been extensively investigated, brain function is not fully dependent on neurons. A recent antemortem autographic study and postmortem RNA sequencing and immunohistochemical studies on aged human brain have investigated the relationship between sleep fragmentation and activation of the innate immune cells of the brain, microglia. In the process of aging, there are marked reductions in the number of brain microglial cells, and the depletion of microglial cells disrupts circadian rhythmicity of brain tissue. We also showed, in a previous study, that pharmacological suppression of microglial function induced sleep abnormalities. However, the mechanism underlying the contribution of microglial cells to sleep homeostasis is only beginning to be understood. This review revisits the impact of aging on the microglial population and activation, as well as microglial contribution to sleep maintenance and response to sleep loss. Most importantly, this review will answer questions such as whether there is any link between senescent microglia and age-related poor quality sleep and how this exacerbates neurodegenerative disease.

Microglial re-modeling contributes to recovery from ischemic injury of rat brain: A study using a cytokine mixture containing granulocyte-macrophage colony-stimulating factor and interleukin-3

“…Thus, it is plausible that cytokine treatment has an anti-apoptotic action in ischemic rat brain by inhibiting microglial expression of pro-inflammatory mediators. Furthermore, the bolstering effects of cytokine treatment on microglial morphology and phagocytosis have been documented in the previous report from our lab ( Fujita et al, 1996 ; Choudhury et al, 2021 ), and this study is the first to present the polarizing effect of cytokine treatment on microglia. Using a hypothesis from a recent review about microglial polarization in the ischemic brain ( Zhang et al, 2021 ) and the evidence from the present study, it appears that microglial remodeling can be effective in treating the ischemic brain ( Figure 6 ).…”

“…Both cytokines used in the present study have been separately investigated for their neuroprotective effects using animal models of various neurological disorders. GM-CSF is an astrocyte-derived cytokine in brain that promotes ramification of microglial cells ( Giulian et al, 1995 ; Fujita et al, 1996 ) and also increases phagocytic activity by microglia ( Choudhury et al, 2021 ). In Alzheimer’s disease brains, IL-3 ameliorates Alzheimer’s disease pathology and cognitive dysfunction, while promoting microglial motility ( McAlpine et al, 2021 ).…”

“…In our previous study with a 6-hydroxydopamine-induced rat PD model, it was found that microglia express higher levels of the GM-CSF receptor than neurons, and neurons express higher levels of the IL-3 receptor than microglia. More interestingly, when primary cultured microglia were treated with both GM-CSF and IL-3, they increased release of neurotrophic factors, as well as phagocytic ability (Choudhury et al, 2011(Choudhury et al, , 2021. Intracarotid injection of GM-CSF increases the number of activated microglia/macrophages and also inhibits cellular apoptosis in the ischemic penumbra after MCAO (Nakagawa et al, 2006).…”

Epidemiology, Physiology and Clinical Approach to Sleepiness at the Wheel in OSA Patients: A Narrative Review

“…Besides OSA, other known causes of EDS are: (1) neurological diseases, such as narcolepsy, idiopathic hypersomnia or Parkinson disease [19,20]; (2) psychiatric disease, especially depression [21]; (3) old age [22]; (4) the use of hypnotics [23]; and (5) diabetes [24]. Sleepiness at the wheel should be specifically investigated, since the risk for car accidents is high in subjects reporting episodes of severe SW [25] and in patients with OSA [26].…”

New Perspectives on Sleep Regulation by Tea: Harmonizing Pathological Sleep and Energy Balance under Stress

“…Astrocytic Gi- and Gq-coupled G-protein-coupled receptor signaling controls NREMS depth and duration, respectively [ 107 , 108 , 109 ]. Depleting microglial cells disrupts the brain tissue’s circadian rhythmicity, increases the duration of NREMS, and reduces hippocampal excitatory neurotransmission in mice [ 110 , 111 ]. Tea protects glial cells under stress.…”