Increasing acetyl‐CoA metabolism attenuates injury and alters spinal cord lipid content in mice subjected to experimental autoimmune encephalomyelitis

Abstract

Acetate supplementation increases brain acetyl-CoA metabolism, alters histone and non-histone protein acetylation, increases brain energy reserves, and is anti-inflammatory and neuroprotective in rat models of neuroinflammation and neuroborreliosis. To determine the impact acetate supplementation has on a mouse model of multiple sclerosis, we quantified the effect treatment had on injury progression, spinal cord lipid content, phospholipase levels, and myelin structure in mice subjected to experimental autoimmune encephalomyelitis (EAE). EAE was induced by inoculating mice with a myelin oligodendrocyte glycoprotein peptide fragment (MOG ), and acetate supplementation was maintained with 4 g/kg glyceryl triacetate by a daily oral gavage. Acetate supplementation prevented the onset of clinical signs in mice subject to EAE compared to control-treated mice. Furthermore, acetate supplementation prevented the loss of spinal cord ethanolamine and choline glycerophospholipid and phosphatidylserine in mice subjected to EAE compared to EAE animals treated with water. Treatment increased saturated and monounsaturated fatty acid levels in phosphatidylserine compared to controls suggesting that acetate was utilized to increase spinal cord fatty acid content. Also, acetate supplementation prevented the loss of spinal cord cholesterol in EAE animals but did not change cholesteryl esters. Treatment significantly increased GD3 and GD1a ganglioside levels in EAE mice when compared to EAE mice treated with water. Treatment returned levels of phosphorylated and non-phosphorylated cytosolic phospholipase A (cPLA ) levels back to baseline and based on FluoroMyelin™ histochemistry maintained myelin structural characteristics. Overall, these data suggest that acetate supplementation may modulate lipid metabolism in mice subjected to EAE.

Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis

“…SCFAs have been found to protect the BBB from oxidative stress via nuclear factor, erythroid 2-like 2 (NFE2L2) signaling [ 46 ] and exert anti-inflammatory and neuroprotective functions [ 47 – 49 ]. Other favorable effects of SCFAs include attenuating myelin injury by increasing brain acetyl-CoA metabolism [ 50 ] and relieving clinical symptoms in EAE mice [ 49 , 50 ]. A zwitterionic capsular polysaccharide A (PSA) produced by Bacteroides fragilis suppresses neuroinflammation by regulating migratory capacity of CD39 + CD4 T cell subsets, thus ameliorates EAE [ 51 ].…”

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

“…In fact, it is noteworthy that oral administration of SCFAs ameliorated the disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS (87,178). Specifically, acetate supplementation is able to induce increased acetyl-CoA metabolism, which increases histone acetylation, resulting in preserved spinal cord lipid content and essentially preventing the onset of clinical symptoms of EAE (179). Furthermore, treatment with butyrate suppresses demyelination and enhances remyelination through oligodendrocyte maturation and differentiation (180).…”

MemBright: a Family of Fluorescent Membrane Probes for Advanced Cellular Imaging and Neuroscience

“…At last MemBright probes combine the capability of the Neurotrace™ dye 9 for neuronal soma and Fluoromyeline™ dye 9 for labelling myelin in spinal cord. 62 Indeed, MemBright stains well the cell soma as well as the dendrites (Fig. 5 and 10), axons (Fig.…”