[
International Worm Meeting,
2021]
The diet of any organism is crucial in providing the energy necessary to not only exist and persist in the environment, but to overcome stress when challenged. One such type of stress comes in the form of Parkinson's disease (PD), which is characterized by the progressive loss of dopaminergic (DA) neuron function and integrity. Although it has been reported and observed that diet type has wide ranging effects on phenotypes in both humans and animal models, the effect that diet has on the progression of DA neuron loss in PD is largely unknown. However, evidence supporting a connection between the brain and the gut microbiome has become increasingly relevant to neurodegenerative diseases. Furthermore, the effect of parental diet on attributes of PD in subsequent generations has not been adequately investigated. The findings of this study indicate that a non-standard diet for Caenorhabditis elegans (C. elegans) has an impact on PD-associated pathology in this animal, in a transgenerational manner. Specifically, feeding worms an alternative bacterial diet of HB101 E. coli, as opposed to the laboratory standard OP50 E. coli, promotes significant, transgenerational protection of DA neurons in response to the stressor and pathological hallmark of PD, a-synuclein (a-syn) overexpression and accumulation. This protection is shown to be dependent on the normal function of Systemic RNA Interference Defective (SID) proteins, including SID-1, SID-2, and SID-3. These proteins are involved in the ability of double-stranded RNAs (dsRNAs) to traverse cellular boundaries, systemically, and silence target genes in C. elegans to varying degrees. Comparative transcriptomic analysis between worms reared on OP50 vs. HB101 E. coli in an a-syn model background has revealed genes and pathways associated with a wide range of processes. These included genes encoding proteins involved in metabolism, cell signaling, development, transcription, stress responses, and transmembrane transport, all of which were observed to be differentially expressed in worms reared on HB101 E. coli. Subsequent functional analysis of select targets by RNA interference revealed the contribution of individual genes to neuroprotection against a-syn-mediated neurodegeneration. This research lays a foundation for future investigation of the subtle distinctions in diet that can impact conserved pathways modulating neuron survival in response to stress.