Table 4.
Microglia regulation of cognitive deficits
| Disease | Experimental models | Main findings | Reference |
|---|---|---|---|
| Aging | C57BL/6 mice; fEPSP and Morris water maze | •Aged mice morphology resembles primed phenotype, with impaired spatial memory and LTP | Elmore et al., 2018 |
| •Microglial inhibition and repopulation reverse cognitive deficits in aged mice | |||
| Aging | Trem2–/– mice; OF, EPM, MWM | •Aged Trem2–/– mice have increased dendritic spine density and learning and memory compared to normal aged mice | Qu and Li, 2020 |
| AD | APP/PS1 mice; CFC | •APP/PSI mice show decreased hippocampal LTP and memory, which are improved with IL-33 | Fu et al., 2016 |
| AD | 5xFAD/TREM2 mice; CFC | •5xFAD/TREM2 mice have attenuated reactive microglia and upregulated phagocytic markers | Lee et al., 2018 |
| •Increased TREM2 gene expression reduces neuronal dystrophy and enhances memory | |||
| AD | Trem2+/– 5XFAD mice | •Trem2+/– 5XFAD mice have decreased compact plaques, increased filamentous plaques, and increased neuronal loss | Yuan et al., 2016 |
| AD | Trem2–/– 5XFAD mice | •Increased autophagy in Trem2–/–5XFAD mice | Ulland et al., 2017 |
| • Cyclocreatine increases number of microglia near plaques and decreases neuronal dystrophy | |||
| TBI | C57BL/6 mice with TBI | •LTP-associated microglia genes Ptpn5, Sqstm1, and Shank3 are significantly upregulated over time in TBI mice | Makinde et al., 2020 |
| TBI | C57B6/J mice; NOR | •Increased microglia numbers and C1q expression in hippocampal CA1 after TBI | Krukowski et al., 2018 |
| •Impaired memory in TBI mice, which is ameliorated by C3–/– KO and anti-C1q antibody | |||
| HAND | Microglia culture from newborn SD rats | •HIV-1 Tat activates NLRP3 which increases proinflammatory cytokines in microglia cells and enhances neurotoxicity and cell death | Rawat et al., 2019 |
| PTSD | Mice; OF, FC, EPM | •Increased microglial numbers, altered activated morphology, and behavioral deficits in PTSD mice | Li et al., 2021 |
| •Deletion and repopulation of microglia rescue behavioral deficits | |||
| Depression | C57BL/6 mice; learned helplessness (LH) paradigm, NOR, Y maze | •LH mice secreted less IL-33, increased microglia activation, and impaired NOR and spatial memory | |
| •PLX5622 and IL-33 improve memory | Worthen et al., 2020 | ||
| Autism | Atg7fl/fl; Lyz2-Cre mice; social interaction, marble burying | •Atg7fl/fl;Lyz2-Cre mice show dysfunction in microglial synaptic pruning, immature and impaired synaptic connectivity, and autistic-like behavior | Kim et al., 2017 |
AD: Alzheimer’s disease; CFC: contextual fear conditioning; EPM: elevated plus maze; fEPSP: field excitatory postsynaptic potential; HAND: HIV-associated neurocognitive disorder; IL-33: interleukin-33; LTP: long-term potentiation; MWM: Morris water maze; NOR: novel object recognition; OF: open field; PTSD: post-traumatic stress disorder; TBI: traumatic brain injury.