Characterizing enteric neurons in dopamine transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content.

Autor: Recinto SJ; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA., Premachandran S; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA., Mukherjee S; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.; Department of Pharmacology and Physiology, Department of Neurosciences, Université de Montreal, Faculty of Medicine, SNC and CIRCA Research Groups, Montreal, Quebec, Canada., Allot A; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada., MacDonald A; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA., Yaqubi M; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA., Gruenheid S; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.; Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada., Trudeau LE; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.; Department of Pharmacology and Physiology, Department of Neurosciences, Université de Montreal, Faculty of Medicine, SNC and CIRCA Research Groups, Montreal, Quebec, Canada., Stratton JA; Department of Neurology and Neurosurgery Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, Maryland, USA.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2024 May; Vol. 59 (10), pp. 2465-2482. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1111/ejn.16307
Abstrakt: The enteric nervous system (ENS) comprises a complex network of neurons whereby a subset appears to be dopaminergic although the characteristics, roles, and implications in disease are less understood. Most investigations relating to enteric dopamine (DA) neurons rely on immunoreactivity to tyrosine hydroxylase (TH)-the rate-limiting enzyme in the production of DA. However, TH immunoreactivity is likely to provide an incomplete picture. This study herein provides a comprehensive characterization of DA neurons in the gut using a reporter mouse line, expressing a fluorescent protein (tdTomato) under control of the DA transporter (DAT) promoter. Our findings confirm a unique localization of DA neurons in the gut and unveil the discrete subtypes of DA neurons in this organ, which we characterized using both immunofluorescence and single-cell transcriptomics, as well as validated using in situ hybridization. We observed distinct subtypes of DAT-tdTomato neurons expressing co-transmitters and modulators across both plexuses; some of them likely co-releasing acetylcholine, while others were positive for a slew of canonical DAergic markers (TH, VMAT2 and GIRK2). Interestingly, we uncovered a seemingly novel population of DA neurons unique to the ENS which was ChAT/DAT-tdTomato-immunoreactive and expressed Grp, Calcb, and Sst. Given the clear heterogeneity of DAergic gut neurons, further investigation is warranted to define their functional signatures and decipher their implication in disease.
(© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: