PMID- 35368277 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220405 IS - 1662-4548 (Print) IS - 1662-453X (Electronic) IS - 1662-453X (Linking) VI - 16 DP - 2022 TI - Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus. PG - 863662 LID - 10.3389/fnins.2022.863662 [doi] LID - 863662 AB - BACKGROUND: The sympathetic nervous system inhibits human colonic motility largely by effects on enteric neurons. Noradrenergic axons, which branch extensively in the myenteric plexus, are integral to this modulatory role, but whether they contact specific types of enteric neurons is unknown. The purpose of this study was to determine the association of noradrenergic varicosities with types of enteric neurons. METHODS: Human colonic tissue from seven patients was fixed and dissected prior to multi-layer immunohistochemistry for human RNA binding proteins C and D (HuC/D) (pan-neuronal cell body labelling), tyrosine hydroxylase (TH, catecholaminergic labelling), Enkephalin (ENK), choline acetyltransferase (ChAT, cholinergic labelling) and/or nitric oxide synthase (NOS, nitrergic labelling) and imaged using confocal microscopy. TH-immunoreactive varicose nerve endings and myenteric cell bodies were reconstructed as three dimensional digital images. Data was exported to a purpose-built software package which quantified the density of varicosities close to the surface of each myenteric cell body. RESULTS: TH-immunoreactive varicosities had a greater mean density within 1 mum of the surface of ChAT +/NOS- nerve cell bodies compared with ChAT-/NOS + cell bodies. Similarly, ENK-immunoreactive varicosities also had a greater mean density close to ChAT +/NOS- cell bodies compared with ChAT-/NOS + cells. CONCLUSION: A method for quantifying close associations between varicosities and nerve cell bodies was developed. Sympathetic axons in the myenteric plexus preferentially target cholinergic excitatory cells compared to nitrergic neurons (which are largely inhibitory). This connectivity is likely to be involved in inhibitory modulation of human colonic motility by the sympathetic nervous system. CI - Copyright (c) 2022 Parker, Wiklendt, Humenick, Chen, Sia, Wattchow, Dinning and Brookes. FAU - Parker, Dominic R AU - Parker DR AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. AD - Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia. FAU - Wiklendt, Lukasz AU - Wiklendt L AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. FAU - Humenick, Adam AU - Humenick A AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. FAU - Chen, Bao Nan AU - Chen BN AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. FAU - Sia, Tiong Cheng AU - Sia TC AD - Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia. FAU - Wattchow, David A AU - Wattchow DA AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. AD - Colorectal Surgical Unit, Division of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia. FAU - Dinning, Phil G AU - Dinning PG AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. FAU - Brookes, Simon J H AU - Brookes SJH AD - Laboratory of Neurogastroenterology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia. LA - eng PT - Journal Article DEP - 20220317 PL - Switzerland TA - Front Neurosci JT - Frontiers in neuroscience JID - 101478481 PMC - PMC8970288 OTO - NOTNLM OT - colon OT - enteric nervous system OT - gastrointestinal motility OT - human OT - myenteric plexus OT - sympathetic nervous system COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/04/05 06:00 MHDA- 2022/04/05 06:01 PMCR- 2022/01/01 CRDT- 2022/04/04 05:06 PHST- 2022/01/27 00:00 [received] PHST- 2022/02/21 00:00 [accepted] PHST- 2022/04/04 05:06 [entrez] PHST- 2022/04/05 06:00 [pubmed] PHST- 2022/04/05 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fnins.2022.863662 [doi] PST - epublish SO - Front Neurosci. 2022 Mar 17;16:863662. doi: 10.3389/fnins.2022.863662. eCollection 2022.