Journal
BRAIN AND BEHAVIOR
Volume 12, Issue 8, Pages -Publisher
WILEY
DOI: 10.1002/brb3.2702
Keywords
anesthesia; ApoE; ApoE fragments; ApoE-knockout mice; ApoE-targeted replacement mice; neurocognition; Tau phosphorylation
Categories
Funding
- National Natural Science Foundation of China [82001149, 82072150]
- Tianjin Health Science and Technology Projects [KJ20023]
- Science and Technology Development Fund of Tianjin Education Commission for Higher Education [2019KJ201]
- Tianjin Natural Science Foundation [20JCQNJC01050]
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Anesthesia-induced Tau phosphorylation and cognitive impairment in young mice, but not adults. Elevated levels of ApoE fragments, rather than full-length ApoE, may contribute to age-dependent cognitive impairment in young mice following sevoflurane anesthesia.
Background Anesthesia induces Tau phosphorylation and cognitive impairment in young, but not adult, mice. Apolipoprotein E (ApoE) may play a protective role in neuronal activity and injury repair, whereas its toxic fragments are reported to induce neurodegeneration and neurocognitive impairment in patients with Alzheimer's disease (AD). Therefore, we set out to test the hypothesis that the difference in ApoE fragments, but not the full-length ApoE, contributes to the difference in Tau phosphorylation and neurocognitive functions following sevoflurane anesthesia in young mice. Methods Sevoflurane was administered to wild-type (WT), ApoE-knockout (ApoE-KO), ApoE3-targeted replacement (ApoE3 expresses both full-length and fragmented ApoE), and ApoE2-targeted replacement (ApoE2 only expresses full-length ApoE) mice. The mRNA and protein levels of ApoE, phosphorylated Tau (pTau), and cognitive function were tested in the mice. Results Sevoflurane anesthesia enhanced ApoE mRNA, total ApoE, full-length ApoE, ApoE fragments, Tau phosphorylation (AT8 and PHF1), and cognitive impairment in young mice, but not in adult mice. ApoE2, but not ApoE3 or ApoE-KO, mice showed reduced sevoflurane-induced pTau elevation and cognitive impairment. Conclusion These data suggest that elevated ApoE fragments rather than full-length ApoE might be one of the underlying mechanisms of age-dependent Tau phosphorylation and cognitive impairment in young mice following sevoflurane anesthesia.
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