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Updated: Aug 6, 2026
Lipidomics and Transcriptomics in Neurological Diseases
Published on: March 18, 2022
Apolipoprotein E deficiency increased microglial activation/CCR3 expression and hippocampal damage in kainic acid
Rui-Sheng Duan1, Zhiguo Chen, Ying-Chun Dou
1Division of Experimental Geriatrics (Novum, plan 5), Karolinska Institutet, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden.
Abstract:
Apolipoprotein E (apoE) down-regulates microglial activation and the secretion of inflammatory molecules in an isoform specific fashion (E2 > E3 > E4); the E4 isoform is over-represented in Alzheimer cases while E2 is under-represented. To better define the role of apoE in neurodegeneration, we contrasted apoE knockout (n = 38) and wild-type mice (n = 41) with respect to seizure activity, mortality, locomotion, hippocampal microglial activation/chemokine receptor expression, and damage to the hippocampus after nasal administration of kainic acid (KA) (water as controls). Mice lacking apoE demonstrated more hunching and less rearing, more damage to neurons in the CA3 region (mean histopathologic score: 3.7 vs. 1.6, p < 0.05), greater microglial activation confirmed by high levels of CD11b and CD86 expression in hippocampus (CD11b p < 0.01, CD86 p < 0.05), and a greater percentage of activated microglia expressing CC chemokine receptors 3 (CCR3) (p < 0.05). Taken together, these findings imply that apoE modulates hippocampal damage induced by KA and found early in the sequence of human Alzheimer's brain changes, by modulating microglial activation.
Insights
Apolipoprotein E (apoE) deficiency exacerbates hippocampal damage and microglial activation following kainic acid administration. This suggests apoE plays a protective role in neurodegeneration by modulating neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
Background:
- Apolipoprotein E (apoE) isoform E4 is linked to Alzheimer's disease, while E2 is under-represented.
- ApoE modulates microglial activation and inflammatory molecule secretion in an isoform-specific manner (E2 > E3 > E4).
Purpose of the Study:
- To investigate the role of apoE in neurodegeneration by comparing apoE knockout and wild-type mice.
- To assess the impact of apoE deficiency on seizure activity, mortality, locomotion, and hippocampal damage after kainic acid (KA) exposure.
Main Methods:
- Comparison of apoE knockout (n=38) and wild-type mice (n=41).
- Assessment of seizure activity, mortality, locomotion, and hippocampal histopathology post-KA administration.
- Analysis of microglial activation markers (CD11b, CD86) and CC chemokine receptor 3 (CCR3) expression in the hippocampus.
Main Results:
- Mice lacking apoE exhibited increased hunching, decreased rearing, and significantly more hippocampal neuronal damage in the CA3 region (3.7 vs. 1.6, p < 0.05).
- ApoE knockout mice showed heightened microglial activation, indicated by elevated CD11b (p < 0.01) and CD86 (p < 0.05) expression.
- A greater percentage of activated microglia expressed CCR3 (p < 0.05) in apoE-deficient mice.
Conclusions:
- Apolipoprotein E plays a crucial role in modulating hippocampal damage induced by kainic acid.
- ApoE deficiency leads to increased microglial activation and exacerbates neurodegeneration.
- These findings suggest apoE's involvement in early Alzheimer's disease-related brain changes through microglial modulation.
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