Non-motor behavioral disorders and the structure of hippocampal neurons in experimental parkinsonism and after administration of human umbilical cord-derived multipotent mesenchymal stromal cells and melatonin
Authors: Labunets I.F. , Panteleymonova T.M. , Mykhalskiy S.A. , Toporova O.K. 
Published: January 2025

Background. The neuroprotective effect of human umbilical cord-derived multipotent mesenchymal stromal cells (hUC-MMSCs) in Parkinson’s disease can depend on the genotype of the recipient and change under the influence of biologically active factors. The purpose was to investigate the effects of transplantation of the hUC-MMSCs as well as their combination with melatonin on indicators of non-motor activity and the structure of hippocampal neurons in mice with an experimental model of parkinsonism, which differ by the H-2 genotype (analogue of human leukocyte antigen). Materials and methods. Adult FVB/N (genotype H-2q) and 129/Sv (genotype H-2b) male mice have received one injection of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin at a dose of 30 mg/kg. Seven days after, the hUC-MMSCs were injected into the tail vein at a dose of 500,000, and from the next day — intraperitoneal melatonin (Sigma, USA) at a dose of 1 mg/kg daily, the course of 14 injections, at 6 p.m. We have evaluated the indicators of non-motor behavior in open field tests (emotional and orientation-exploratory activity), the development of the conditioned reaction of passive avoidance (cognitive function) and the structure of hippocampal neurons. Results. In mice of both strains under the influence of MPTP, the orientation-exploratory and cognitive activities have been suppressed, the emotional activity has been increased and the structure of neurons in the CA1 region and the dentate gyrus has been disturbed. Transplantation of hUC-MMSCs has improved the indicators of orientation-exploratory and cognitive functions in FVB/N mice and the emotional activity in 129/Sv mice. An activating effect of cells on some indicators of emotional behavior (the number of acts of grooming) in mice of both strains has been revealed. The number of pathologically changed neurons in the CA1 region and dentate gyrus in mice of both strains has decreased after transplantation of hUC-MMSCs. Injections of melatonin after the administration of cells have led to the strengthening of their positive effect on the cognitive function in FVB/N mice and on the emotional activity in 129/Sv mice and have also neutralized their negative effects on the number of acts of grooming in mice of both strains. In the hippocampus of such mice, there was a marked restoration of the cytoarchitectonics and morphometric indicators. At the same time, the positive effect of a combination of hUC-MMSCs and melatonin has been more pronounced in 129/Sv mice. Conclusions. Manifestations of the influence of transplanted hUC-MMSCs and their combination with melatonin on the functional state of the nervous system and the structure of hippocampal neurons of mice with a model of parkinsonism largely depend on their H-2 genotype. The results can be the basis for the development of personalized cell therapy for this pathology using hUC-MMSCs.