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Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer’s disease
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Abstract
Female Alzheimer’s disease (AD) patients display greater cognitive deficits and worse AD pathology as compared to male AD patients. In this study, we found that conditional knockout (cKO) of
Atg5
in female microglia failed to obtain disease-associated microglia (DAM) gene signatures in familiar AD mouse model (5xFAD). Next, we analyzed the maintenance and neurogenesis of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ) from 5xFAD mice with
Atg5
cKO. Our data indicated that
Atg5
cKO reduced the NSC number in hippocampus of female but not male 5xFAD mice. However, in the SVZ,
Atg5
cKO only impaired NSCs in male 5xFAD mice. Interestingly, female 5xFAD;
Fip200
cKO mice and 5xFAD;
Atg14
cKO mice did not show NSC defects. These autophagy genes cKO 5xFAD mice exhibited a higher neurogenesis activity in their SVZ. Together, our data indicate a sex-specific role for microglial
Atg5
in postnatal neurogenesis in AD mice.
Springer Science and Business Media LLC
Title: Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer’s disease
Description:
Abstract
Female Alzheimer’s disease (AD) patients display greater cognitive deficits and worse AD pathology as compared to male AD patients.
In this study, we found that conditional knockout (cKO) of
Atg5
in female microglia failed to obtain disease-associated microglia (DAM) gene signatures in familiar AD mouse model (5xFAD).
Next, we analyzed the maintenance and neurogenesis of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ) from 5xFAD mice with
Atg5
cKO.
Our data indicated that
Atg5
cKO reduced the NSC number in hippocampus of female but not male 5xFAD mice.
However, in the SVZ,
Atg5
cKO only impaired NSCs in male 5xFAD mice.
Interestingly, female 5xFAD;
Fip200
cKO mice and 5xFAD;
Atg14
cKO mice did not show NSC defects.
These autophagy genes cKO 5xFAD mice exhibited a higher neurogenesis activity in their SVZ.
Together, our data indicate a sex-specific role for microglial
Atg5
in postnatal neurogenesis in AD mice.
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