Amelioration of hippocampal dysfunction by adipose tissue-targeted stem cell transplantation in a mouse model of type 2 diabetes.
Balaji KrishnanHanaa S SallamBatbayar TumurbataarSalvatore SaievaDa'Marcus BaymonDemidmaa TuvdendorjMaria-Adelaide MicciNicola AbateGiulio TaglialatelaPublished in: Journal of neurochemistry (2020)
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.
Keyphrases
- adipose tissue
- insulin resistance
- cerebral ischemia
- type diabetes
- stem cell transplantation
- high fat diet
- high frequency
- high fat diet induced
- cognitive impairment
- mesenchymal stem cells
- polycystic ovary syndrome
- glycemic control
- mouse model
- temporal lobe epilepsy
- transcranial magnetic stimulation
- subarachnoid hemorrhage
- high dose
- prefrontal cortex
- metabolic syndrome
- cell therapy
- oxidative stress
- skeletal muscle
- cardiovascular disease
- open label
- fatty acid
- double blind
- randomized controlled trial
- multiple sclerosis
- cell cycle
- umbilical cord
- white matter
- clinical trial
- cell proliferation
- diabetic rats
- stem cells
- signaling pathway
- weight loss
- working memory
- drug induced