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Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats
Li Zhang1, Chao Li1, Rui Huang1
1Department of Neurology, Henry Ford Hospital, Detroit, MI, United States.
Frontiers in Aging Neuroscience
|August 1, 2022
Summary
Diabetes-induced small extracellular vesicles (sEVs) impair brain function and neurogenesis. Healthy sEVs, however, can reverse these effects, improving cognitive function and brain health in diabetic rats.
Area of Science:
- Neuroscience
- Endocrinology
- Cell Biology
Background:
- Diabetes mellitus (DM) causes cognitive decline and dementia risk by impairing cerebral vascular function and neurogenesis.
- The role of small extracellular vesicles (sEVs) in DM-induced brain complications remains unclear.
- Cerebral endothelial cell-derived sEVs (CEC-sEVs) are investigated for their involvement in DM-related neurological deficits.
Purpose of the Study:
- To investigate the role of CEC-sEVs in DM-induced cerebral vascular dysfunction and neurogenesis impairment.
- To evaluate the therapeutic potential of normal CEC-sEVs (N-CEC-sEVs) in ameliorating cognitive deficits in aged DM rats.
Main Methods:
- Comparison of sEVs from diabetic (DM-CEC-sEVs) and normal (N-CEC-sEVs) rats.
- Assessment of neurogenesis, neuroblast generation, and cerebral endothelial function.
- In vivo studies involving intravenous administration of N-CEC-sEVs in aged DM rats.
- Analysis of miRNA and protein changes within recipient cells after N-CEC-sEVs uptake.
- Investigation of cellular uptake mechanisms (clathrin and caveolin dependent endocytosis).
Main Results:
- DM-CEC-sEVs inhibited neural stem cell (NSC) neurogenesis and impaired cerebral endothelial function.
- Treatment with N-CEC-sEVs improved cognitive function, enhanced neurogenesis, and restored cerebral vascular function in aged DM rats.
- Administered N-CEC-sEVs crossed the blood-brain barrier, were internalized by NSCs, and modulated specific miRNA and protein levels (miR-1, miR-146a, IRAK-M, TSP-1).
- N-CEC-sEVs uptake was mediated by clathrin and caveolin dependent endocytosis.
Conclusions:
- DM-CEC-sEVs contribute to cerebral vascular dysfunction and neurogenesis impairment in diabetes.
- N-CEC-sEVs demonstrate therapeutic potential for improving cognitive function in aged DM rats by restoring vascular and neurogenic functions.
- This study highlights the therapeutic value of CEC-sEVs in managing diabetes-associated cognitive decline.
