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. Author manuscript; available in PMC: 2020 Mar 7.
Published in final edited form as: Mol Cell. 2018 Dec 4;73(5):1001–1014.e8. doi: 10.1016/j.molcel.2018.11.028

Fig 4-. αS expression alters lipid metabolism in rat and C. elegans synucleinopathy models.

Fig 4-

A) Lipid profiles of human αS expression in rat cortical neurons. Lipid species (516) are indicated by color and in the order of the key on the right of the map. B) αS expression increases LD formation in rat cortical neurons. Microscopy-Green: BODIPY (LDs); Red: αS. Blue: Hoechst (nucleus). Neurons were imaged at 14d (ImageJ quantified). Bar chart: integrated density signal fold difference for MOI1 vs MOI5. n=16 cells. p<0.0001,t-test. C) LDs protect against αS toxicity in rat cortical neurons. Neuronal survival was measured following expression of αS in control rat cortical neurons and in neurons with knockdown of DGAT1 and DGAT2 (D1+D2). Fig S3E, RTPCR knockdown data. % Viability (Resazurin to Resorufin conversion). n=6. ****p<0.0001 *p=0.02 (one way Anova). D) Reduction in LPIN expression suppresses αS toxicity in rat cortical neurons. Neuronal survival was measured following expression of αS in control rat cortical neurons and in neurons with knockdown of LPIN1, LPIN2, LPIN3. Fig S3F, RTPCR knockdown data. %Viability (Resazurin to Resorufin conversion). n=6 ****p<0.0001 **p=0.007 (one way Anova). E) OA content is increased upon human αs expression in rat cortical neurons. Intracellular FA analysis was performed in control and human αS expressing rat cortical neurons. *p=0.02, t-test. F) Reduction in SCD1 rescues αS toxicity. Neuronal survival was measured following expression of human αS in control rat cortical neurons and in neurons with SCD1 knockdown. Fig S4E, RT-PCR knockdown data. % Viability (Resazurin to Resorufin conversion). n=6. ****p<0.0001 (one way Anova). G) Inhibition of SCD1 rescues αS toxicity (% ATP). Survival of neurons was measured following treatment with SCD1 inhibitor in control and human αS-expressing rat cortical neurons. ****p<0.0001 ***p≤0.0005 (one way Anova). H) SCD1 inhibition rescues DGAT1+DGAT2+αS-associated toxicity in rat cortical neurons. DGAT1 and DGAT2 (D1+D2) were knocked down in control vs human αS-expressing rat cortical neurons + DMSO or SCD inhibitor. %Viability (Resazurin to Resorufin conversion). n=6. ***p<0.0005 (one way Anova). I) SCD knockdown in a C. elegans model of dopaminergic neuron degeneration rescued an αS-induced dopaminergic neuron degeneration phenotype. Open arrowheads-CEP dendrites (white), ADE dendrites (black);closed arrowheads-CEP cell bodies (white), ADE cell bodies (black); *p<0.05.