Immunoreactivity of Kir3.1, muscarinic receptors 2 and 3 on the brainstem, vagus nerve and heart tissue under experimental demyelination

Akyuz E., DOĞANYİĞİT Z., Okan A., YILMAZ S., UÇAR S., Akın A. T.

Brain Research Bulletin, vol.197, pp.13-30, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 197
  • Publication Date: 2023
  • Doi Number: 10.1016/j.brainresbull.2023.03.009
  • Journal Name: Brain Research Bulletin
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Psycinfo, Veterinary Science Database
  • Page Numbers: pp.13-30
  • Keywords: Cuprizone, Multiple sclerosis, Muscarinic acetylcholine receptor, Potassium channel
  • Yozgat Bozok University Affiliated: Yes


Aims: Demyelination affects the propogation of neuronal action potential by slowing down the progression. This process results in a neuro-impairment like Multiple Sclerosis (MS). Evidence show that MS also contributes to involvement of the autonomic system. In the molecular approach to this involvement, we aimed to observe muscarinic ACh receptor 2–3 (mAChR2–3), and inwardly rectifying potassium channel 3.1 (Kir3.1) immunoreactivities on the brainstem, vagus nerve, and heart under cuprizone model. Main methods: Wistar albino rats were randomly divided into 8 groups; duplicating 4 groups as male and female: control groups (n = 3 +3), Cuprizone groups (n = 12 +12), sham groups (n = 4 +4), and carboxy-methyl-cellulose groups (n = 3 +3). Cuprizone-fed rats underwent demyelination via Luxol fast blue (LFB) staining of the hippocampus (Gyrus dentatus and Cornu Ammonis) and cortex. Immunohistochemistry analysis followed to the pathologic measurement of the brainstem, vagus nerve, and heart for mAChR2, mAChR3 and Kir3.1 proteins Key findings: A significant demyelination was observed in the hippocampus and cortex tissues of rats in the female and male cuprizone groups. Myelin basic protein immunoreactivity demonstrated that cuprizone groups, in both males and females, had down-regulation in the hippocampus and cortex areas. The weights of the cuprizone-fed rats significantly decreased over six weeks. Dilated blood vessels and neuronal degeneration were severe in the hippocampus and cortex of the cuprizone groups. In the female cuprizone group, expression of mAChR2 and mAChR2 was significantly increased in the brainstem, atrium/ventricle of heart, and left/right sections of vagus nerve. Kir3.1 channels were also up-regulated in the left vagus nerve and heart sections of the female cuprizone group Significance: Especially in our data where female-based significant results were obtained reveal that demyelination may lead to significant mAChR2, mAChR3 and Kir3.1 changes in brainstem, vagus nerve, and heart. A high immunoreactive response to demyelination at cholinergic centers may be a new target