A diet rich in docosahexaenoic acid enhances reactive astrogliosis and ramified microglia morphology in apolipoprotein E epsilon 4-targeted replacement mice

Hillary Chappus-McCendie; Marc-Antoine Poulin; Raphaël Chouinard-Watkins; Milène Vandal; Frédéric Calon; Marc-Antoine Lauzon; Mélanie Plourde

doi:10.1016/j.nbas.2022.100046

A diet rich in docosahexaenoic acid enhances reactive astrogliosis and ramified microglia morphology in apolipoprotein E epsilon 4-targeted replacement mice

Aging Brain. 2022 Jul 25:2:100046. doi: 10.1016/j.nbas.2022.100046. eCollection 2022.

Authors

Hillary Chappus-McCendie^{1

2

3}, Marc-Antoine Poulin⁴, Raphaël Chouinard-Watkins^{1

2

3

5}, Milène Vandal^{5

6}, Frédéric Calon^{5

6}, Marc-Antoine Lauzon^{1

4}, Mélanie Plourde^{1

2

3

5

7}

Affiliations

¹ Centre de Recherche sur le Vieillissement, CIUSSS de l'Estrie-CHUS, Sherbrooke, QC, Canada.
² Département de pharmacologie-physiologie, Université de Sherbrooke, Sherbrooke, QC, Canada.
³ Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁴ Département de génie chimique et de génie biotechnologique, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁵ Institut de la nutrition et des aliments fonctionnels, Université Laval, Québec, QC, Canada.
⁶ Faculté de pharmacie et centre de recherche du CHU de Québec-Université Laval, QC, Canada.
⁷ Département de Médecine, Université de Sherbrooke, Sherbrooke, QC, Canada.

Abstract

Docosahexaenoic acid (DHA) consumption reduces spatial memory impairment in mice carrying the human apolipoprotein E ε4 (APOE4) allele. The current study evaluated whether astrocyte and microglia morphology contribute to the mechanism of this result. APOE3 and APOE4 mice were fed either a DHA-enriched diet or a control diet from 4 to 12 months of age. Coronal brain sections were immunostained for GFAP, Iba1, and NeuN. Astrocytes from APOE4 mice exhibited signs of reactive astrogliosis compared to APOE3 mice. Consumption of DHA exacerbated reactive astrocyte morphology in APOE4 carriers. Microglia from APOE4-control mice exhibited characteristics of amoeboid morphology and other characteristics of ramified morphology (more processes, greater process complexity, and greater distance between neighboring microglia). DHA enhanced ramified microglia morphology in APOE4 mice. In addition, APOE4 mice fed the DHA diet had lower hippocampal concentrations of interleukin-7, lipopolysaccharide-induced CXC chemokine and monocyte chemoattractant protein 1, and higher concentration of interferon-gamma compared to APOE4-control mice. Our results indicate that a diet rich in DHA enhances reactive astrogliosis and ramified microglia morphology in APOE4 mice.

Keywords: APOE2, apolipoprotein E epsilon 2 allele; APOE3, apolipoprotein E epsilon 3 allele; APOE4, apolipoprotein E epsilon 4 allele; Apolipoprotein E epsilon 4; Astrocyte; DHA, docosahexaenoic acid; Docosahexaenoic acid; EPA, eicosapentaenoic acid; Microglia; Neuroinflammation; PUFA, polyunsaturated fatty acids.