Astrocytic ApoE underlies maturation of hippocampal neurons and cognitive recovery after traumatic brain injury in mice.

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Cognition* ; Neurogenesis*; Apolipoproteins E/*genetics ; Brain Injuries, Traumatic/*physiopathology ; Neurons/*pathology; Animals ; Apolipoproteins E/metabolism ; Astrocytes/metabolism ; Disease Models, Animal ; Female ; Hippocampus/pathology ; Male ; Mice ; Mice, Knockout

Polymorphisms in the apolipoprotein E (ApoE) gene confer a major genetic risk for the development of late-onset Alzheimer's disease (AD) and are predictive of outcome following traumatic brain injury (TBI). Alterations in adult hippocampal neurogenesis have long been associated with both the development of AD and recovery following TBI and ApoE is known to play a role in this process. In order to determine how ApoE might influence hippocampal injury-induced neurogenesis, we generated a conditional knockout system whereby functional ApoE from astrocytes was ablated prior to injury. While successfully ablating ApoE just prior to TBI in mice, we observed an attenuation in the development of the spines in the newborn neurons. Intriguingly, animals with a double-hit, i.e. injury and ApoE conditionally inactivated in astrocytes, demonstrated the most pronounced impairments in the hippocampal-dependent Morris water maze test, failing to exhibit spatial memory after both acquisition and reversal training trials. In comparison, conditional knockout mice without injury displayed impairments but only in the reversal phase of the test, suggesting accumulative effects of astrocytic ApoE deficiency and traumatic brain injury on AD-like phenotypes. Together, these findings demonstrate that astrocytic ApoE is required for functional injury-induced neurogenesis following traumatic brain injury.
(© 2021. The Author(s).)

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R01 NS095803 United States NS NINDS NIH HHS; R56 NS089523 United States NS NINDS NIH HHS; T35 AG044303 United States AG NIA NIH HHS

0 (Apoe protein, mouse)
0 (Apolipoproteins E)

Date Created: 20211119 Date Completed: 20211224 Latest Revision: 20220201

20231215

PMC8602391

10.1038/s42003-021-02841-4

34795427