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Dietary n-3 PUFAs deficiency increases vulnerability to inflammation-induced spatial memory impairment

Abstract : Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.
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https://hal.inrae.fr/hal-02640350
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Submitted on : Thursday, May 28, 2020 - 2:28:15 PM
Last modification on : Thursday, July 15, 2021 - 3:36:02 PM

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Jean-Christophe Delpech, Aurore Thomazeau, Charlotte Madore, Clementine Bosch-Bouju, Thomas Larrieu, et al.. Dietary n-3 PUFAs deficiency increases vulnerability to inflammation-induced spatial memory impairment. Neuropsychopharmacology, Nature Publishing Group, 2015, 40 (12), pp.2774-2787. ⟨10.1038/npp.2015.127⟩. ⟨hal-02640350⟩

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