Ukr.Biochem.J. 2022; Volume 94, Issue 2, Mar-Apr, pp. 57-65
doi: https://doi.org/10.15407/ubj94.02.057
Changes in the expression of TRPV4 and TRPM8 channels in the colon of rats with 6-OHDA-induced Parkinson’s disease
V. О. Stetska1, T. V. Dovbynchuk1, N. V. Dziubenko2,
A. V. Zholos1, G. M. Tolstanova2*
1ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
2Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: ganna.tolstanova@knu.ua
Received: 01 June 2022; Accepted: 01 July 2022
Parkinson’s disease (PD) is neurodegenerative disease, which is accompanied by degeneration of dopaminergic neurons in subtantia nigra. Non-motor symptoms, in particular, disorders of the gastrointestinal (GI) tract are observed in 20-80% of patients some 15-20 years before clinically diagnosed PD and are not a least important feature of PD pathogenesis. The transient receptor potential (TRP) channels are expressed throughout the GI tract, where they play an important role in taste, thermoregulation, pain, mucosal function and homeostasis, control of interstitial motility etc. The aim of this study was to investigate the contribution of TRPV4 and TRPM8 channels in the GI motor function in the colon of rats with PD, incduced by injection of the 12 μg 6-hydroxydopamine (6-OHDA). The studies were performed on the 4th week and the 7th month after PD induction The rats were randomly divided into: I group – the sham-lesioned rats, 4 μl 0.9% NaCl, autopsy 4 weeks after injection (n = 5); II group – the 6-OHDA-PD rats, 4 μl 12 μg of 6-OHDA, autopsy 4 weeks after injection (n = 5); III group – the sham-lesioned rats, 4 μl 0.9% NaCl, autopsy 7 months after injection (n = 4); IV group – the 6-OHDA-PD rats, 4 μl 12 μg of 6-OHDA, autopsy 7 months after injection (n = 5). We evaluated the body weight of rats, GI transit time, the cecum weight index and immunohistochemical identification of tyrosine hydroxylase (TH) -positive cells, and TRPV4, TRPM8 expression in rat’s colon. We showed that on the 7th month of the experiment, the GI transit time doubles over time; the cecum weight index of 6-OHDA rats increased by 57%; the number of TH-positive cells in colon rats decreased 2-fold, while TRPM8 ion channels were downregulated in PD rats and TRPV4 ion channels were upregulated in the colon of rats with 6-OHDA-PD. It was concluded that TRPV4 and TRPM8 ion channels may be considered pharmacological targets in the progression of PD pathology.
Keywords: 6-OHDA, colon, motility, transit time, TRPM8 channels, TRPV4 channels
References:
- Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386(9996):896-912. PubMed, CrossRef
- Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat Disord. 2011;17(1):10-15. PubMed, CrossRef
- Herath M, Hosie S, Bornstein JC, Franks AE, Hill-Yardin EL. The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders. Front Cell Infect Microbiol. 2020;10:248. PubMed, PubMedCentral, CrossRef
- Pedrosa Carrasco AJ, Timmermann L, Pedrosa DJ. Management of constipation in patients with Parkinson’s disease. NPJ Parkinsons Dis. 2018;4:6.
PubMed, PubMedCentral,CrossRef - Williams-Gray CH, Worth PF. Parkinson’s disease. Medicine. 2016;44(9):542-546. CrossRef
- Van Kampen JM, Baranowski DC, Robertson HA, Shaw CA, Kay DG. The Progressive BSSG Rat Model of Parkinson’s: Recapitulating Multiple Key Features of the Human Disease. PLoS One. 2015;10(10):e0139694. PubMed, PubMedCentral, CrossRef
- Lama J, Buhidma Y, Fletcher EJR, Duty S. Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research. Neuronal Signal. 2021;5(4):NS20210026. PubMed, PubMedCentral, CrossRef
- Lima AC, Meurer YSR, Bioni VS, Cunha DMG, Gonçalves N, Lopes-Silva LB, Becegato M, Soares MBL, Marinho GF, Santos JR, Silva RH. Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson’s Disease. Front Aging Neurosci. 2021;13:757714. PubMed, PubMedCentral, CrossRef
- Michalick L, Kuebler WM. TRPV4-A Missing Link Between Mechanosensation and Immunity. Front Immunol. 2020;11:413. PubMed, PubMedCentral, CrossRef
- Cenac N, Bautzova T, Le Faouder P, Veldhuis NA, Poole DP, Rolland C, Bertrand J, Liedtke W, Dubourdeau M, Bertrand-Michel J, Zecchi L, Stanghellini V, Bunnett NW, Barbara G, Vergnolle N. Quantification and Potential Functions of Endogenous Agonists of Transient Receptor Potential Channels in Patients With Irritable Bowel Syndrome. Gastroenterology. 2015;149(2):433-444.e7. PubMed, CrossRef
- Luo J, Qian A, Oetjen LK, Yu W, Yang P, Feng J, Xie Z, Liu S, Yin S, Dryn D, Cheng J, Riehl TE, Zholos AV, Stenson WF, Kim BS, Hu H. TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells. Immunity. 2018;49(1):107-119.e4. PubMed, PubMedCentral, CrossRef
- Amato A, Terzo S, Lentini L, Marchesa P, Mulè F. TRPM8 Channel Activation Reduces the Spontaneous Contractions in Human Distal Colon. Int J Mol Sci. 2020;21(15):5403. PubMed, PubMedCentral, CrossRef
- Matsumoto K, Kato S. TRPV4 regulates vascular endothelial permeability during colonic inflammation in dextran sulphate sodium-induced murine colitis. Nihon Yakurigaku Zasshi. 2018;152(4):170-174. PubMed, CrossRef
- Stetska VO, Dovbynchuk TV, Makedon YS, Dziubenko NV. The effect of water-soluble pristine C60 fullerene on 6-OHDA-induced Parkinson’s disease in rats. Regul Mech Biosyst. 2021; 12(4):599-607. CrossRef
- Stetska VO, Moroz OF, Dovbynchuk TV, Tolstanova GM, Zholos AV. The Role of TRPV4 Cation Channels in Smooth Muscle Contractile Activity in Rats. Ukr Z Med Bіol Sportu. 2020; 5(6):370-377. CrossRef
- Aiello M, Eleopra R, Rumiati RI. Body weight and food intake in Parkinson’s disease. A review of the association to non-motor symptoms. Appetite. 2015;84:204-211. PubMed, CrossRef
- Ma K, Xiong N, Shen Y, Han C, Liu L, Zhang G, Wang L, Guo S, Guo X, Xia Y, Wan F, Huang J, Lin Z, Wang T. Weight Loss and Malnutrition in Patients with Parkinson’s Disease: Current Knowledge and Future Prospects. Front Aging Neurosci. 2018;10:1. PubMed, PubMedCentral, CrossRef
- Zucca A, Segura-Aguilar J, Ferrari E, Muñoz P, Paris I, Sulzer D, Sarna T, Casella L, Zecca L. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog Neurobiol. 2017;155:96-119. PubMed, PubMedCentral, CrossRef
- Graff J, Brinch K, Madsen JL. Gastrointestinal mean transit times in young and middle-aged healthy subjects. Clin Physiol. 2001;21(2):253-259. PubMed, CrossRef
- Rhee KJ, Wu S, Wu X, Huso DL, Karim B, Franco AA, Rabizadeh S, Golub JE, Mathews LE, Shin J, Sartor RB, Golenbock D, Hamad AR, Gan CM, Housseau F, Sears CL. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009r;77(4):1708-1718. PubMed, PubMedCentral, CrossRef
- Loesche WJ. Effect of bacterial contamination on cecal size and cecal contents of gnotobiotic rodents. J Bacteriol. 1969;99(2):520-526. PubMed, PubMedCentral, CrossRef
- Killinger B, Labrie V. The Appendix in Parkinson’s Disease: From Vestigial Remnant to Vital Organ? J Parkinsons Dis. 2019;9(s2):S345-S358. PubMed, PubMedCentral, CrossRef
- Shultz JM, Resnikoff H, Bondarenko V, Joers V, Mejia A, Simmons H, Emborg ME. Neurotoxin-Induced Catecholaminergic Loss in the Colonic Myenteric Plexus of Rhesus Monkeys. J Alzheimers Dis Parkinsonism. 2016;6(6):279. PubMed, PubMedCentral, CrossRef
- Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, Quigley EM. Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet. 1995;346(8979):861-864. PubMed, CrossRef
- Harrington AM, Hughes PA, Martin CM, Yang J, Castro J, Isaacs NJ, Blackshaw AL, Brierley SM. A novel role for TRPM8 in visceral afferent function. Pain. 2011;152(7):1459-1468. PubMed, CrossRef
- Ramachandran R, Hyun E, Zhao L, Lapointe TK, Chapma K, Hirota CL, Ghosh S, McKemy DD, Vergnolle N, Beck PL, Altier C, Hollenberg MD. TRPM8 activation attenuates inflammatory responses in mouse models of colitis. Proc Natl Acad Sci USA. 2013;110(18):7476-7481. PubMed, PubMedCentral, CrossRef
- Mustafa S, Oriowo M. Cooling-induced contraction of the rat gastric fundus: mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho-kinase activation. Clin Exp Pharmacol Physiol. 2005;32(10):832-838. PubMed, CrossRef
- Ambort D, Johansson MEV, Gustafsson JK, Nilsson HE, Ermund A, Johansson BR, Koeck PJB, Hebert H, Hansson GC. Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc Natl Acad Sci USA. 2012;109(15):5645-5650. PubMed, PubMedCentral,CrossRef
- Holzer P. TRP channels in the digestive system. Curr Pharm Biotechnol. 2011;12(1):24-34. PubMed, PubMedCentral,CrossRef
- Yamawaki H, Mihara H, Suzuki N, Nishizono H, Uchida K, Watanabe S, Tominaga M, Sugiyama T. Role of transient receptor potential vanilloid 4 activation in indomethacin-induced intestinal damage. Am J Physiol Gastrointest Liver Physiol. 2014;307(1):G33-G40. PubMed, CrossRef
- Sukumaran P, Sun Y, Schaar A, Selvaraj S, Singh BB. TRPC Channels and Parkinson’s Disease. Adv Exp Med Biol. 2017;976:85-94. PubMed, PubMedCentral, CrossRef
- D’Aldebert E, Cenac N, Rousset P, Martin L, Rolland C, Chapman K, Selves J, Alric L, Vinel JP, Vergnolle N. Transient receptor potential vanilloid 4 activated inflammatory signals by intestinal epithelial cells and colitis in mice. Gastroenterology. 2011;140(1):275-285. PubMed, CrossRef
This work is licensed under a Creative Commons Attribution 4.0 International License.