1. Amelioration of hippocampal dysfunction by adipose tissue‐targeted stem cell transplantation in a mouse model of type 2 diabetes
- Author
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Da’Marcus Baymon, Batbayar Tumurbataar, Nicola Abate, Giulio Taglialatela, Balaji Krishnan, Hanaa S. Sallam, Demidmaa Tuvdendorj, Maria-Adelaide Micci, and Salvatore Saieva
- Subjects
Leptin ,0301 basic medicine ,medicine.medical_specialty ,Long-Term Potentiation ,Adipose tissue ,Mice, Transgenic ,Fatty Acids, Nonesterified ,Hippocampal formation ,Diet, High-Fat ,Mesenchymal Stem Cell Transplantation ,Hippocampus ,Synaptic Transmission ,Biochemistry ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Adipocyte ,Internal medicine ,medicine ,Animals ,Humans ,Pyrophosphatases ,biology ,Phosphoric Diester Hydrolases ,business.industry ,Mesenchymal Stem Cells ,Long-term potentiation ,medicine.disease ,Mice, Inbred C57BL ,Transplantation ,Insulin receptor ,030104 developmental biology ,Endocrinology ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,chemistry ,biology.protein ,Insulin Resistance ,business ,030217 neurology & neurosurgery - Abstract
There is growing evidence that type 2 diabetes or insulin resistance is linked to cognitive impairment. We recently confirmed altered lipid composition, down-regulation of insulin receptor expression and impaired basal synaptic transmission in the hippocampus of our transgenic murine model of adipocyte insulin resistance (AtENPP1-Tg). Here we evaluated whether the correction of adipose tissue dysfunction [via the subcutaneous transplantation of mesenchymal stem cells (MSC)] can improve the hippocampal synaptic transmission in AtENPP1-Tg mice versus their wildtype littermates. Animals were simply randomized to receive MSC, then weighed weekly for 12 weeks. At euthanasia, we assessed leptin in the collected serum and hippocampal synaptic high-frequency stimulation long-term potentiation (HFS-LTP) using brain slices. MSC transplantation normalized AtENPP1-Tg body and epididymal fat weights and was associated with increased leptin levels, a sign of adipocyte maturation. More importantly, transplantation restored the deficiency observed in AtENPP1-Tg HFS-LTP, the cellular readout of memory. Our results further corroborate the role of adipocyte maturation arrest in adipose tissue and highlight a role for the adipose tissue in modulating hippocampal cellular mechanisms. Further studies are warranted to explore the mechanisms for the MSC-induced improvement of hippocampal HFS-LTP.
- Published
- 2020