# COG1410 Alleviated Chronic Sleep Deprivation-Induced Memory Loss by Regulating Microglial Phagocytosis and Inhibiting Hippocampal Inflammation

## TL;DR

A peptide called COG1410 helps prevent memory loss from sleep deprivation by reducing brain inflammation and improving microglial function.

## Contribution

COG1410 was shown to rescue memory consolidation by regulating microglial phagocytosis and hippocampal inflammation in sleep-deprived mice.

## Key findings

- Sleep deprivation increased microglial phagocytosis of synapses and reduced mature synapses, impairing long-term memory.
- COG1410 pretreatment rescued memory consolidation by reducing microglial phagocytosis and promoting anti-inflammatory M2 polarization.
- TREM2 downregulation reduced COG1410's protective effects, suggesting its role in the mechanism.

## Abstract

It is widely recognized that sleep loss harms healthy
adults. Microglia-mediated
synaptic pruning is active during sleep and contributes to memory
consolidation. Here, we established a mouse model of sleep deprivation
(SD) using a modified multiple-platform method (MMPM). Using western
blotting, immunofluorescence, and Golgi-Cox staining, we found that
SD increased microglial capacity for phagocytizing mature synapses
and decreased the number of mature synapses, which affected long-term
memory consolidation but did not affect working memory after SD. Further,
we discovered that pretreatment with the APOE mimic peptide COG1410
could partially rescue SD-induced long-term memory consolidation.
Regarding the mechanism, COG1410 alleviated SD-induced abnormal microglial
phagocytosis and increased the number of mature synapses. Also, COG1410
promoted M2 polarization of microglia and reduced hippocampal inflammation
caused by SD. However, whether the anti-inflammatory effect of COG1410
is related to the regulation of microglial phagocytosis still needs
further study. Finally, we downregulated the expression of TREM2 in
the hippocampus using small interfering RNA (siRNA), which reduced
the protective effect of COG1410 in SD mice. In summary, COG1410 has
the potential to prevent SD-induced memory consolidation impairment
by maintaining microglial phagocytosis and anti-inflammation in the
mouse hippocampus.