Articles

  • the Korean Society for Brain and Neural Sciences

Article

Original Article

Exp Neurobiol 2021; 30(4): 285-293

Published online August 11, 2021

https://doi.org/10.5607/en21022

© The Korean Society for Brain and Neural Sciences

Region-Specific Differences in the Apoe4-dependent Response to Focal Brain Injury

Sung Eun Lee1,2†, Haijie Yang3†, Youngjun Sung4, Younghoon Kim1 and Sun Ah Park1,2,5*

1Lab for Neurodegenerative Dementia, Department of Anatomy, Ajou University School of Medicine, 2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, 3Department of Pharmacology, Ajou University School of Medicine, 4Department of Biological Science, Ajou University, 5Department of Neurology, Ajou University School of Medicine, Suwon 16499, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-31-219-5030, FAX: 82-31-219-5039
e-mail: sap001@ajou.ac.kr
These authors contributed equally to this article.

Received: June 23, 2021; Revised: July 16, 2021; Accepted: August 4, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Apolipoprotein E (apoE) plays a role in various physiological functions including lipid transport, synaptic plasticity, and immune modulation. Epidemiological studies suggest that the apoE4 allele increases the risk of post-traumatic sequelae. This study was performed to investigate regionspecific effects of the apoE4 isoform on post-traumatic neurodegeneration. Two focal brain injuries were introduced separately in the motor cortex and hippocampus of apoE4 knock-in, apoE3 knock-in, apoE knockout, and wild-type (WT) mice. Western blotting showed that the expression levels of pre-synaptic and post-synaptic markers at the recovery stage were lower in the hippocampal injury core in apoE4 mice, compared with apoE3 and WT mice. Fast glial activation (determined by immunohistochemistry with glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and cluster of differentiation 45 antibodies) was characteristic of apoE4 mice with hippocampal injury penumbra. apoE4-specific changes were not observed after cortical injury. The intensity of microglial activation in the hippocampus was inversely correlated with the volume of injury reduction on sequential magnetic resonance imaging examinations, when validated using matched samples. These findings indicate that the effects of the interaction between apoE4 and focal brain damage are specific to the hippocampus. Manipulation of inflammatory cell responses could be beneficial for reducing post-traumatic hippocampal neurodegeneration in apoE4 carriers.

Graphical Abstract


Keywords: Apolipoprotein E4, Neuroglia, Hippocampus, Inflammation, Brain injuries, Neurodegeneration