Tag Archives: 6-OHDA
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.
Systemic inflammation biomarkers in 6-OHDA- and LPS-induced Parkinson’s disease in rats
Zh. Oliynyk*, M. Rudyk, V. Svyatetska, T. Dovbynchuk, G. Tolstanova, L. Skivka
ESC “Institute of Biology and Medicine”, Taras Shevchenko National University of Kyiv, Ukraine;
*e-mail: ojankin@yahoo.com
Received: 14 December 2021; Accepted: 21 January 2022
Hematological and immunological markers of systemic inflammation were studied in 6-hydroxydopamine (6-OHDA)- and lipopolysaccharide (LPS)-induced models of Parkinson’s disease (PD). Experiments were carried out on adult male Wistar rats: 1 – intact animals; 2 – sham-operated animals and 3 – 6-OHDA- and LPS-lesioned animals. PD development was confirmed by the results of behavioral testing (apomorphine test, open field test) and immunohistochemical detection of the loss of dopaminergic neurons. Hematological indices (complete blood count and differential leukocyte count (DLC)) were examined using hematological analyser. Immunological indices included phenotypic (CD206 and CD80/86) and metabolic (oxidative metabolism and phagocytic activity) characteristics of circulating monocytes (Mo) and granulocytes (Gr), which were determined by flow cytometry, as well as plasma levels of C-reactive protein, which were determined by ELISA. LPS-induced PD was associated with neutrophilia, 1.9 times increased neutrophil-to-lymphocyte ratio, 3 times increased platelet-to-lymphocyte ratio, and 3 times increased systemic immune inflammation index as compared to intact animals. Functional profile of circulating phagocytes from LPS-lesioned animals was characterized by the pro-inflammtory metabolic shift, as was indicated by 5 times increased oxidative metabolism indices and up-regulated CD80/86 expression along with decreased phagocytic activity and CD206 expression. 6-OHDA-lesioned rats demonstrated decreased DLC indices as compared to intact and sham-operated rats. Functional profile of circulating phagocytes in this model was characterized by anti-inflammatory shift. The results obtained from this study demonstrated that stereotaxic LPS-induced PD is appropriate rodent model for the study of systemic inflammation which is inherent for the disease pathophysiology.