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Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice.

Abstract

BACKGROUND

Neuroinflammation is a proposed mechanism by which Alzheimer's disease (AD) pathology potentiates neuronal death and cognitive decline. Consumption of omega-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of AD in human observational studies and exerts protective effects on cognition and pathology in animal models. These fatty acids and molecules derived from them are known to have anti-inflammatory and pro-resolving properties, presenting a potential mechanism for these protective effects.

METHODS

Here, we explore this mechanism using fat-1 transgenic mice and their wild type littermates weaned onto either a fish oil diet (high in n-3 PUFA) or a safflower oil diet (negligible n-3 PUFA). The fat-1 mouse carries a transgene that enables it to convert omega-6 to omega-3 PUFA. At 12 weeks of age, mice underwent intracerebroventricular (icv) infusion of amyloid-β 1-40. Brains were collected between 1 and 28 days post-icv, and hippocampal microglia, astrocytes, and degenerating neurons were quantified by immunohistochemistry with epifluorescence microscopy, while microglia morphology was assessed with confocal microscopy and skeleton analysis.

RESULTS

Fat-1 mice fed with the safflower oil diet and wild type mice fed with the fish oil diet had higher brain DHA in comparison with the wild type mice fed with the safflower oil diet. Relative to the wild type mice fed with the safflower oil diet, fat-1 mice exhibited a lower peak in the number of labelled microglia, wild type mice fed with fish oil had fewer degenerating neurons, and both exhibited alterations in microglia morphology at 10 days post-surgery. There were no differences in astrocyte number at any time point and no differences in the time course of microglia or astrocyte activation following infusion of amyloid-β 1-40.

CONCLUSIONS

Increasing brain DHA, through either dietary or transgenic means, decreases some elements of the inflammatory response to amyloid-β in a mouse model of AD. This supports the hypothesis that omega-3 PUFA may be protective against AD by modulating the immune response to amyloid-β.

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  • Authors+Show Affiliations

    ,

    Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, ON, M5S 3E2, Canada.

    ,

    Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, ON, M5S 3E2, Canada.

    ,

    Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, ON, M5S 3E2, Canada.

    Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College St., Room 306, Toronto, ON, M5S 3E2, Canada. richard.bazinet@utoronto.ca.

    Source

    Journal of neuroinflammation 13:1 2016 Sep 29 pg 257

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    27688126

    Citation

    Hopperton, Kathryn E., et al. "Brain Omega-3 Polyunsaturated Fatty Acids Modulate Microglia Cell Number and Morphology in Response to Intracerebroventricular Amyloid-β 1-40 in Mice." Journal of Neuroinflammation, vol. 13, no. 1, 2016, p. 257.
    Hopperton KE, Trépanier MO, Giuliano V, et al. Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice. J Neuroinflammation. 2016;13(1):257.
    Hopperton, K. E., Trépanier, M. O., Giuliano, V., & Bazinet, R. P. (2016). Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice. Journal of Neuroinflammation, 13(1), p. 257.
    Hopperton KE, et al. Brain Omega-3 Polyunsaturated Fatty Acids Modulate Microglia Cell Number and Morphology in Response to Intracerebroventricular Amyloid-β 1-40 in Mice. J Neuroinflammation. 2016 Sep 29;13(1):257. PubMed PMID: 27688126.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Brain omega-3 polyunsaturated fatty acids modulate microglia cell number and morphology in response to intracerebroventricular amyloid-β 1-40 in mice. AU - Hopperton,Kathryn E, AU - Trépanier,Marc-Olivier, AU - Giuliano,Vanessa, AU - Bazinet,Richard P, Y1 - 2016/09/29/ PY - 2016/07/21/received PY - 2016/09/13/accepted PY - 2016/10/1/entrez PY - 2016/10/1/pubmed PY - 2016/10/1/medline KW - Alzheimer’s disease KW - Amyloid-β KW - Microglia KW - Neuroinflammation KW - Omega-3 polyunsaturated fatty acids SP - 257 EP - 257 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 13 IS - 1 N2 - BACKGROUND: Neuroinflammation is a proposed mechanism by which Alzheimer's disease (AD) pathology potentiates neuronal death and cognitive decline. Consumption of omega-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of AD in human observational studies and exerts protective effects on cognition and pathology in animal models. These fatty acids and molecules derived from them are known to have anti-inflammatory and pro-resolving properties, presenting a potential mechanism for these protective effects. METHODS: Here, we explore this mechanism using fat-1 transgenic mice and their wild type littermates weaned onto either a fish oil diet (high in n-3 PUFA) or a safflower oil diet (negligible n-3 PUFA). The fat-1 mouse carries a transgene that enables it to convert omega-6 to omega-3 PUFA. At 12 weeks of age, mice underwent intracerebroventricular (icv) infusion of amyloid-β 1-40. Brains were collected between 1 and 28 days post-icv, and hippocampal microglia, astrocytes, and degenerating neurons were quantified by immunohistochemistry with epifluorescence microscopy, while microglia morphology was assessed with confocal microscopy and skeleton analysis. RESULTS: Fat-1 mice fed with the safflower oil diet and wild type mice fed with the fish oil diet had higher brain DHA in comparison with the wild type mice fed with the safflower oil diet. Relative to the wild type mice fed with the safflower oil diet, fat-1 mice exhibited a lower peak in the number of labelled microglia, wild type mice fed with fish oil had fewer degenerating neurons, and both exhibited alterations in microglia morphology at 10 days post-surgery. There were no differences in astrocyte number at any time point and no differences in the time course of microglia or astrocyte activation following infusion of amyloid-β 1-40. CONCLUSIONS: Increasing brain DHA, through either dietary or transgenic means, decreases some elements of the inflammatory response to amyloid-β in a mouse model of AD. This supports the hypothesis that omega-3 PUFA may be protective against AD by modulating the immune response to amyloid-β. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/27688126/Brain_omega_3_polyunsaturated_fatty_acids_modulate_microglia_cell_number_and_morphology_in_response_to_intracerebroventricular_amyloid_β_1_40_in_mice_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-016-0721-5 DB - PRIME DP - Unbound Medicine ER -