Fig. 1: UA promotes neuronal health across generations.
From: An intestinal sphingolipid confers intergenerational neuroprotection
a,b, Schematics (top) and fluorescence micrographs (bottom) of posterior lateral mechanosensory left (PLML) anatomy in wild-type (a) and mec-17(ok2109); lon-2(e678) (b) animals expressing the Pmec-4::gfp transgene (zdIs5). Left lateral view, anterior to the left. Scale bars, 25 μm. b, A typical PLM axon break (red line) observed in adult (3-d-old) mec-17(ok2109); lon-2(e678) animals is indicated. c, Chemical structure of UA. d, Adult mec-17(ok2109); lon-2(e678) F1 animals exposed to UA (50 μM) from P0 L4 to day 3 of F1 had reduced PLM axon breaks. e, Timeline of UA exposure. The stages of C. elegans development relevant to UA exposure in the P0 and F1 generations are shown (top). Vertical dashed line, demarcation between the P0 and F1 generations. f, Continuous UA exposure (P0 L4 larva to F1 adult) reduces PLM axon breaks in mec-17(ok2109); lon-2(e678) animals. Specifically, UA exposure of P0 animals from the L4 larval stage to adult (ii), but not earlier (i) or later ((iii) and (iv)) stages results in a reduction in PLM axon breaks in mec-17(ok2109); lon-2(e678) animals. g, Experimental scheme for the intergenerational inheritance experiment. P0 animals (L4 larvae) were treated with DMSO (control) or UA for 16 h. Animals of each generation were allowed to lay eggs on untreated plates for 3 h and the adults (3-d-old) were assessed for axon breaks. h, The progeny of mec-17(ok2109); lon-2(e678) P0 mothers exposed to UA for 16 h (L4 to young adult) have reduced PLM axon breaks for two generations (F1 and F2). d,f,h, n = 101 and 103 (d); f, n = 249, 199, 173, 151, 166 and 107 (f); and n = 126, 128, 103, 128, 77 and 97 (h) hermaphrodite animals per condition (left to right). P values were determined using a one-way analysis of variance (ANOVA; f) or unpaired Student’s t-test (d,h). ****P ≤ 0.0001; ***P ≤ 0.001; **P ≤ 0.01; and NS, not significant. Error bars indicate the s.e.m. Source data are provided.
