Open AccessDHA modulates MANF and TREM2 abundance, enhances neurogenesis, reduces infarct size, and improves neurological function after experimental ischemic stroke
Author(s) -
Belayev Ludmila,
Hong SungHa,
Freitas Raul S.,
Menghani Hemant,
Marcell Shawn J.,
Khoutorova Larissa,
Mukherjee Pranab K.,
Reid Madigan M.,
Oria Reinaldo B.,
Bazan Nicolas G.
Publication year - 2020
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13444
Subject(s) - trem2 , neuroprotection , neurotrophic factors , penumbra , microglia , brain derived neurotrophic factor , astrocyte , neurogenesis , dentate gyrus , medicine , receptor , downregulation and upregulation , pharmacology , endocrinology , chemistry , microbiology and biotechnology , biology , inflammation , ischemia , biochemistry , central nervous system , gene
Aims Mesencephalic astrocyte‐derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells‐2; TREM2) regulates the production of pro‐ and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; MANF and TREM2 expression was measured by immunohistochemistry and Western blotting. Results MANF was upregulated in neurons and astrocytes on days 1, 7, and 14, and TREM2 was expressed on macrophages in the ischemic penumbra and dentate gyrus (DG) on days 7 and 14. DHA improved neurobehavioral recovery, attenuated infarct size on days 7 and 14, increased MANF and decreased TREM2 expression in ischemic core, penumbra, DG, and enhanced neurogenesis on Day 14. Conclusion MANF and TREM2 protein abundance is robustly increased after MCAo, and DHA treatment potentiated MANF abundance, decreased TREM2 expression, improved neurobehavioral recovery, reduced infarction, and provided enhanced neuroprotection.