Sex-Related Abnormalities in Substantia Nigra Lipids in Parkinson's Disease

Abstract

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.

Keywords: Parkinson’s disease; gangliosides; myelin; neurodegeneration; sex differences.

Figure 1.

(a) HPTLC of gangliosides in substantia nigra (SN) samples from male control and PD subjects. The amount of ganglioside sialic acid spotted per lane was equivalent to approximately 1.5 µg. The plate was developed by a single ascending run with CHCl₃:CH₃OH:dH₂O (55:45:10 by vol) containing 0.02% CaCl₂·2H₂O. The bands were visualized with the resorcinol-HCl spray, as described previously (Hauser et al., 2004). HPTLC of SN neutral lipids (b) and acidic lipids (c) in male control and PD subjects. The amount of neutral lipids and acidic lipids spotted per lane was equivalent to approximately 35 µg and 100 µg tissue dry weight, respectively. The plates were developed as we described previously (Baek et al., 2009). The second PD sample in (c) was moved to its position from another region on the same HPTLC, which explains the merge line seen on the plate. Neutral lipids include: CE = cholesteryl esters; TG = triglycerides; IS = internal standard; C = cholesterol; Cer = ceramide; CB = cerebrosides (doublet); PE = phosphatidylethanolamine; PC = phosphatidylcholine; SM = sphingomyelin. As the zwitterionic lipids (PC, PE, and SM) elute with the neutral lipids, they are included in this group. Acidic lipids include: FA = fatty acids; IS = internal standard; CL = cardiolipin; PA = phosphatidic acid; SULF = sulfatides (doublet); PS = phosphatidylserine; PI = phosphatidylinositol.