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

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Title: Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content.
Authors: Recinto, Sherilyn Junelle (AUTHOR), Premachandran, Shobina (AUTHOR), Mukherjee, Sriparna (AUTHOR), Allot, Alexis (AUTHOR), MacDonald, Adam (AUTHOR), Yaqubi, Moein (AUTHOR), Gruenheid, Samantha (AUTHOR), Trudeau, Louis‐Eric (AUTHOR), Stratton, Jo Anne (AUTHOR)
Source: European Journal of Neuroscience. May2024, Vol. 59 Issue 10, p2465-2482. 18p.
Subjects: Dopaminergic neurons, Submucous plexus, Enteric nervous system, Dopamine receptors, Tyrosine hydroxylase, Fluorescent proteins, In situ hybridization
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
  Group: Ti
  Data: Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content.
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  Label: Authors
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  Data: <searchLink fieldCode="AR" term="%22Recinto%2C+Sherilyn+Junelle%22">Recinto, Sherilyn Junelle</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Premachandran%2C+Shobina%22">Premachandran, Shobina</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mukherjee%2C+Sriparna%22">Mukherjee, Sriparna</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Allot%2C+Alexis%22">Allot, Alexis</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22MacDonald%2C+Adam%22">MacDonald, Adam</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yaqubi%2C+Moein%22">Yaqubi, Moein</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gruenheid%2C+Samantha%22">Gruenheid, Samantha</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Trudeau%2C+Louis‐Eric%22">Trudeau, Louis‐Eric</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Stratton%2C+Jo+Anne%22">Stratton, Jo Anne</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. May2024, Vol. 59 Issue 10, p2465-2482. 18p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Dopaminergic+neurons%22">Dopaminergic neurons</searchLink><br /><searchLink fieldCode="DE" term="%22Submucous+plexus%22">Submucous plexus</searchLink><br /><searchLink fieldCode="DE" term="%22Enteric+nervous+system%22">Enteric nervous system</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine+receptors%22">Dopamine receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Tyrosine+hydroxylase%22">Tyrosine hydroxylase</searchLink><br /><searchLink fieldCode="DE" term="%22Fluorescent+proteins%22">Fluorescent proteins</searchLink><br /><searchLink fieldCode="DE" term="%22In+situ+hybridization%22">In situ hybridization</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ejn.16307
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      – Code: eng
        Text: English
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        PageCount: 18
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      – SubjectFull: Dopaminergic neurons
        Type: general
      – SubjectFull: Submucous plexus
        Type: general
      – SubjectFull: Enteric nervous system
        Type: general
      – SubjectFull: Dopamine receptors
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      – SubjectFull: Tyrosine hydroxylase
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      – SubjectFull: Fluorescent proteins
        Type: general
      – SubjectFull: In situ hybridization
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      – TitleFull: Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content.
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            – D: 15
              M: 05
              Text: May2024
              Type: published
              Y: 2024
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