Parkinson’s disease (PD) is a neurodegenerative movement disorder involving the selective loss of dopamine-producing neurons in the substantia nigra (SN). Differences in disease presentation, prevalence, and age of onset have been reported between males and females with PD. The content and composition of the major glycosphingolipids, phospholipids, and cholesterol were evaluated in the SN from 12 PD subjects and in 18 age-matched, neurologically normal controls. Total SN ganglioside sialic acid content and water content (%) were significantly lower in the male PD subjects than in the male controls. The content of all major gangliosides were reduced in the male PD subjects to some degree, but the neuronal-enriched gangliosides, GD1a and GT1b, were most significantly reduced. The distribution of phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol was also significantly lower in the male PD subjects than in the male controls. However, the distribution of myelin-enriched cerebrosides and sulfatides was significantly higher in the male PD subjects than in the male controls suggesting myelin sparing in the male PD subjects. No elevation was detected for astrocytosis-linked GD3. These neurochemical changes provide evidence of selective neuronal loss in SN of the males with PD without robust astrocytosis. In contrast to the SN lipid abnormalities found in the male PD subjects, no significant abnormalities were found in the female PD subjects for SN water content or for any major SN lipids. These data indicate sex-related differences in SN lipid abnormalities in PD.

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.