PMID- 33815140 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210406 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 12 DP - 2021 TI - Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model. PG - 628107 LID - 10.3389/fphys.2021.628107 [doi] LID - 628107 AB - Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-alpha), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-alpha, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression. CI - Copyright (c) 2021 Amin, Sharawy, El Tablawy, Elberry, Youssef, Abdelhady, Rashed and Hassan. FAU - Amin, Shaimaa Nasr AU - Amin SN AD - Department of Basic Medical Sciences, Faculty of Medicine, The Hashemite University, Zarqa, Jordan. AD - Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Sharawy, Nivin AU - Sharawy N AD - Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - El Tablawy, Nashwa AU - El Tablawy N AD - Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Elberry, Dalia Azmy AU - Elberry DA AD - Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Youssef, Mira Farouk AU - Youssef MF AD - Department of Histology, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Abdelhady, Ebtehal Gamal AU - Abdelhady EG AD - Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt. FAU - Rashed, Laila Ahmed AU - Rashed LA AD - Department of Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt. FAU - Hassan, Sherif Sabry AU - Hassan SS AD - Department of Medical Education, School of Medicine, California University of Science and Medicine, San Bernardino, CA, United States. AD - Department of Anatomy, Faculty of Medicine, Cairo University, Cairo, Egypt. LA - eng PT - Journal Article DEP - 20210318 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC8012759 OTO - NOTNLM OT - cognition OT - diabetes OT - melatonin OT - stem cells OT - synaptic plasticity 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- 2021/04/06 06:00 MHDA- 2021/04/06 06:01 PMCR- 2021/03/18 CRDT- 2021/04/05 05:56 PHST- 2020/11/16 00:00 [received] PHST- 2021/02/11 00:00 [accepted] PHST- 2021/04/05 05:56 [entrez] PHST- 2021/04/06 06:00 [pubmed] PHST- 2021/04/06 06:01 [medline] PHST- 2021/03/18 00:00 [pmc-release] AID - 10.3389/fphys.2021.628107 [doi] PST - epublish SO - Front Physiol. 2021 Mar 18;12:628107. doi: 10.3389/fphys.2021.628107. eCollection 2021.