# The Function of Microglia in Cognitive Impairment Influenced by Sleep Deprivation

**Authors:** Jiping Jiang, Min Li, Yulong Xia, Wei Wei, Sheng Li, Xiao Wu, Sen Li, Houping Xu

PMC · DOI: 10.1007/s10571-025-01654-x · Cellular and Molecular Neurobiology · 2026-01-14

## TL;DR

This paper reviews how sleep deprivation affects microglia, leading to cognitive impairment, and explores potential treatment strategies.

## Contribution

The paper provides a comprehensive overview of microglial mechanisms in sleep deprivation-induced cognitive decline and suggests therapeutic directions.

## Key findings

- Sleep deprivation impacts microglia through pathways like Aβ plaque deposition and neuroinflammation.
- Microglia have dual roles in both worsening and alleviating cognitive impairment.
- The review identifies possible treatment strategies targeting microglial function.

## Abstract

Sleep deprivation, resulting from factors such as lifestyle, disease, or environmental influences, directly contributes to cognitive decline. Research has found that the impact of sleep deprivation on microglia may be a key factor in cognitive impairment. The specific mechanisms through which microglia contribute to this process are not yet fully understood. It may act through multiple pathways, including the accumulation of excitatory neurotransmitters, Aβ plaque deposition, neuroinflammation, disrupted autophagy, abnormal cell death, and impaired synaptic plasticity. This review synthesizes evidence from the past two decades on the interplay between microglia, sleep deprivation, and cognitive impairment. It provides a comprehensive overview of associated factors and their operational pathways, analyzes the network of pathological interactions, and identifies possible treatment directions. It also emphasizes the dual functions of microglia in worsening and alleviating cognitive impairment while investigating possible therapeutic strategies targeting microglial function. This review aims to clarify microglial pathways in sleep-loss-related cognitive deficits, thereby advancing the field and providing a foundation for new therapeutic strategies.

## Full-text entities

- **Genes:** Casp7 (caspase 7) [NCBI Gene 12369] {aka CMH-1, ICE-IAP3, Mch3, caspase-7, mCASP-7}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Arg1 (arginase, liver) [NCBI Gene 11846] {aka AI, Arg-1, PGIF}, Diablo (diablo, IAP-binding mitochondrial protein) [NCBI Gene 66593] {aka 0610041G12Rik, 1700006L01Rik, Smac}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Casp9 (caspase 9) [NCBI Gene 12371] {aka APAF-3, CASP-9, Caspase-9, ICE-LAP6, Mch6}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Apaf1 (apoptotic peptidase activating factor 1) [NCBI Gene 11783] {aka 6230400I06Rik, Apaf-1, Apaf1l, fog, mKIAA0413}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, S100a8 (S100 calcium binding protein A8 (calgranulin A)) [NCBI Gene 20201] {aka 60B8Ag, B8Ag, CFAg, CP-10, Caga, MRP8}, Cx3cr1 (C-X3-C motif chemokine receptor 1) [NCBI Gene 13051] {aka mCX3CR1}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, CRYAB (crystallin alpha B) [NCBI Gene 1410] {aka CMD1II, CRYA2, CTPP2, CTRCT16, HEL-S-101, HSPB5}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}, TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Htra2 (HtrA serine peptidase 2) [NCBI Gene 64704] {aka Omi, Prss25, mnd2}, Irf3 (interferon regulatory factor 3) [NCBI Gene 54131] {aka C920001K05Rik, IRF-3}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, CHRNA7 (cholinergic receptor nicotinic alpha 7 subunit) [NCBI Gene 1139] {aka CHRNA7-2, NACHRA7, a7nAChR, nAChR7}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cd33 (CD33 molecule) [NCBI Gene 12489] {aka Siglec-3, gp67}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Bax (BCL2-associated X protein) [NCBI Gene 12028], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, C1QA (complement C1q A chain) [NCBI Gene 712] {aka C1QD1}, AIF1 (allograft inflammatory factor 1) [NCBI Gene 199] {aka AIF-1, IBA1, IRT-1, IRT1}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}
- **Diseases:** inflammation (MESH:D007249), autism (MESH:D001321), central nervous system diseases (MESH:D002493), BBB (MESH:C536830), insomnia (MESH:D007319), PD (MESH:D010300), Huntington's disease (MESH:D006816), Insufficient sleep (MESH:D012892), synaptic dysfunction (MESH:C536122), synaptic impairment (MESH:D012183), behavioral deficits (MESH:D019958), multiple sclerosis (MESH:D009103), sleep disorder (MESH:D012893), CI (MESH:D003072), death (MESH:D003643), AD (MESH:D000544), Neurological Dysfunction (MESH:D009461), depression (MESH:D003866), amyloid (MESH:C000718787), neurological injury (MESH:D020196), brain inflammation (MESH:D004660), ADHD (MESH:D001289), synapse loss (MESH:D016388), neural hyperactivity (MESH:D006948), sleep restriction (MESH:D002313), cancer (MESH:D009369), neuronal damage (MESH:D009410), Neurotoxicity (MESH:D020258), dementia (MESH:D003704), neurodegeneration (MESH:D019636), behavioral disorders (MESH:D001523), glutamate excitotoxicity (MESH:C537425), Neuroinflammation (MESH:D000090862), schizophrenia (MESH:D012559)
- **Chemicals:** propofol (MESH:D015742), GABA (MESH:D005680), ROS (MESH:D017382), ATP (MESH:D000255), QUIN (MESH:D017378), SCFAs (MESH:D005232), antioxidative (-), PHA-543613 (MESH:C513163), dopamine (MESH:D004298), tryptophan (MESH:D014364), acetylcholine (MESH:D000109), KYN (MESH:D007737), rapamycin (MESH:D020123), adrenaline (MESH:D004837), Glutamate (MESH:D018698)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12868487