Fig. 4: HA-114 fatty acids extracts, but not proteins, are sufficient to rescue paralysis.
Transgenics were monitored from the adult stage, scored daily for paralysis and fed with control OP50 or HA-114’s individual components. a Mutant FUS worms fed with heat-killed L. rhamnosus HA-114 did not show paralysis phenotypes when compared to worms fed with OP50. b Protein extract from L. rhamnosus HA-114 failed to rescue age-dependent paralysis in ALS worm models. c When compared to fatty acid extract from OP50, fatty acids extract from HA-114 suppressed paralysis phenotypes in FUS animals. d 40 μM of Etomoxir, a cpt-1/CPT1 inhibitor, increased paralysis in FUS transgenics. e The same concentration was not enough to block neuroprotective effects of L. rhamnosus HA-114, when compared to worms fed with OP50. f mRNA expression of cpt-1 was significantly decreased in FUSS57Δ worms when compared to FUSWT animals. g mRNA expression of CPT1A was significantly decreased in livers of SOD1G93A mice when compared to livers of Non-Tg animals. h Decrease expression of two transcripts related to carnitine palmitoyltransferase (CHKB_CPT1B and CPT1C) is observed in C9ORF72 patients when compared to controls. No significant change is observed in sporadic ALS. Data: GEO accession: GSM1642314; SRA study: SRP05647760. For paralysis assays (a–e) curves were generated and compared using the log-rank (Mantel–Cox) test. a: Alive OP50 n = 275; Heat-killed OP50 n = 212; Alive HA-114 n = 246; Heat-killed HA-114 n = 259. b: OP50 proteins n = 238; HA-114 proteins n = 240. c: OP50 fatty acids n = 240; HA-114 fatty acids n = 220. d: OP50 n = 220; Etomoxir n = 240. e: OP50 n = 326; HA-114 n = 302. For TaqMan assays (f, g), an unpaired t test was performed. f: n = 5 per condition. g: n = 3 per condition. For boxplots, minimum, first quartile, third quartile, and maximum are shown.
