Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

Autor: Roushdy MMS; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Labib JMW; Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Abdelrahim DS; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Department of Pharmacology, Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt., Mohamed DAW; Department of Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Abdelmalak MFL; Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Department of Pharmacology, Faculty of Medicine, Modern University for Technology and Information, Cairo, Egypt.
Jazyk: angličtina
Zdroj: Cell biology international [Cell Biol Int] 2024 Sep; Vol. 48 (9), pp. 1326-1342. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1002/cbin.12200
Abstrakt: Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.
(© 2024 International Federation of Cell Biology.)
Databáze: MEDLINE