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Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal-Glial Synapses and Reduced Expression in NlgnR451C Mice
Herath, M.; Cho, E.; Marklund, U.; Franks, A.E.; Bornstein, J.C.; Hill-Yardin, E.L. Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal–Glial Synapses and Reduced Expression in Nlgn3R451C Mice. Biomolecules2023, 13, 1063.
Herath, M.; Cho, E.; Marklund, U.; Franks, A.E.; Bornstein, J.C.; Hill-Yardin, E.L. Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal–Glial Synapses and Reduced Expression in Nlgn3R451C Mice. Biomolecules 2023, 13, 1063.
Herath, M.; Cho, E.; Marklund, U.; Franks, A.E.; Bornstein, J.C.; Hill-Yardin, E.L. Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal–Glial Synapses and Reduced Expression in Nlgn3R451C Mice. Biomolecules2023, 13, 1063.
Herath, M.; Cho, E.; Marklund, U.; Franks, A.E.; Bornstein, J.C.; Hill-Yardin, E.L. Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal–Glial Synapses and Reduced Expression in Nlgn3R451C Mice. Biomolecules 2023, 13, 1063.
Abstract
Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but cellular Nlgn3 expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization for Nlgn3 mRNA and immunofluorescence for cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells. We measured Nlgn3 mRNA neuronal and glial expression via quantitative 3-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single cell RNA sequencing (scRNASeq) data to assess for Nlgn3, Nlgn1, Nlgn2 and their binding partners, Nrxn1-3, MGDA1 and MGDA2, in enteric neural subsets. Most submucosal and myenteric neurons expressed Nlgn3 mRNA. In contrast to other Nlgns and binding partners, Nlgn3 was strongly expressed in enteric glia, suggesting a role for Neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces Nlgn3 mRNA expression in cholinergic but not VIPergic submucosal neurons. In the myenteric plexus, Nlgn3 mRNA levels are reduced in calretinin and NOS labelled neurons and S100ß labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in Nlgn3, which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.
Biology and Life Sciences, Neuroscience and Neurology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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