Aggregation of alpha-synuclein in enteric neurons does not impact function in vitro.

Autor: Bindas AJ; Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 339 Mugar, Boston, MA, 02115, USA., Nichols KN; Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 339 Mugar, Boston, MA, 02115, USA., Roth NJ; Geriatrics Section, Department of Medicine, Boston Medical Center, One Boston Medical Center Pl., Boston, MA, 02118, USA., Brady R; Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 339 Mugar, Boston, MA, 02115, USA., Koppes AN; Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 339 Mugar, Boston, MA, 02115, USA. a.koppes@northeastern.edu.; Department of Biology, Northeastern University, 360 Huntington Ave., 340 Mugar, Boston, MA, 02115, USA. a.koppes@northeastern.edu., Koppes RA; Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., 339 Mugar, Boston, MA, 02115, USA. r.koppes@northeastern.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Dec 23; Vol. 12 (1), pp. 22211. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1038/s41598-022-26543-x
Abstrakt: Recent evidence implicates a gut-first pathogenesis in the enteric nervous system (ENS) within a portion of PD patients, yet in vitro investigations have primarily focused on the central nervous system. Here, the preformed fibril (PFF) PD model is applied with co-administered groups of butyrate and lipopolysaccharide to model the effects of the local gut microbiome. Significant PFF uptake and retention occur in isolated rat enteric neurons compared to untreated controls resulting in increasing immunostained aggregate conformation-specific, alpha-synuclein (a-Syn) average intensity between 6 µg PFF and untreated controls. Cortical neurons significantly retain PFFs with an increase in aggregated a-Syn average intensity within all dosages. Differences in growth cone morphology but not dynamics in PFF-treated ENS cultures occur. Electrophysiological recordings via a microelectrode array (MEA) indicate no overall difference in spontaneous spike rate. However, only untreated controls respond to PD-relevant dopamine stimulus, while 1 µg PFF and control populations respond to stimulus with ENS-abundant acetylcholine. Finally, no differences in substance P levels-correlated with PD and neurodegeneration-are observed. Overall, these findings suggest the ENS retains PFF dosage absent acute loss in function, however, does experience changes in growth cone morphology and dopamine-stimulated activity.
(© 2022. The Author(s).)
Databáze: MEDLINE
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