ArticlebioRxiv : the preprint server for biology2024
Sex specific effects of environmental toxin-derived alpha synuclein on enteric neuronal-epithelial interactions.
Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Parkinson's Disease (PD) is a neurodegenerative disorder with prodromal gastrointestinal (GI) issues often emerging decades before motor symptoms. Pathologically, PD can be driven by accumulation of misfolded alpha synuclein (aSyn) protein in the brain and periphery, including the GI tract. Disease epidemiology differs by sex, with men twice as likely to develop PD. Women, however, experience faster disease progression, higher mortality, and more severe GI symptoms. Gut calcitonin gene related peptide (CGRP) is a key regulator of intestinal contractions and visceral pain. The current study tests the hypothesis that sex differences in GI symptomology in PD are the result of aSyn aggregation altering enteric CGRP signaling pathways. Methods: To facilitate peripheral aSyn aggregation, the pesticide rotenone was administered intraperitoneally once daily for two weeks to male and female mice. Mice were sacrificed two weeks after the last rotenone injection and immunohistochemistry was performed on sections of proximal colon. Key Results: Levels of aSyn were heightened in myenteric plexus neurons and a subset of neurons immunoreactive to CGRP in rotenone treated mice. Female mice exhibited 153% more myenteric aSyn, 26% more apical CGRP immunoreactivity, and 66.7% more aSyn in apical CGRP Conclusions: This study used a mouse model of PD to uncover sex specific alterations in enteric neuronal and epithelial populations, underscoring the importance of considering sex as a biological variable while investigating prodromal GI symptoms. KEY POINTS: Mouse model of Parkinson's Disease (PD) was used to investigate sex specific impact of enteric alpha synuclein (aSyn) on colonic goblet cells and CGRP
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