Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFA) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) have shown beneficial effects on learning and memory, neuroinflammatory processes and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-archidonoylglycerol (2-AG) are the most widely studied endocannabinoids, and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair

Early morphofunctional plasticity of microglia in response to acute lipopolysaccharide

International audienceWithin the central nervous system (CNS) the traditional role of microglia has been in brain infection and disease, phagocytosing debris and secreting factors to modify disease progression. This led to the concept of “resting” versus “activated” microglia. However, this is misleading because multiple phenotypic and morphological stages of microglia can influence neuronal structure and function in any condition and recent evidence extends their role to healthy brain homeostasis. The present work was thus aimed at reappraising the concept of morphofunctional activity of microglia in a context of peripheral acute immune challenge, where microglial activity is known to be modified, using the new state-of-the-art techniques available. To do so, mice were injected peripherally with lipopolysaccharide, a potent inducer of cerebral inflammation, and we assessed early cytokines production, phenotype, motility and morphology of microglial cells. Our results showed that LPS induced a widespread inflammatory response both peripherally and centrally, as revealed by the quantification of cytokines levels. We also found an alteration of microglial motility that was confirmed by in vivo studies showing an overall reduction of microglial processes length in the hippocampus of LPS-treated animals. Finally, analysis of various surface receptors expression revealed that LPS did not significantly impact microglial phenotype 2 h after the injection but rather induced an increase of CD11b+/CD45high cells. These latter may be at the vasculature, at the CNS vicinity, or may have invaded the CNS