METHODS: The locomotor activity, learning, and memory were assessed by using open field test and water T-maze test. This study also examined changes in neuronal cell morphology using cresyl violet and apoptosis staining. We also performed immunohistochemical study to analyse the expression of the glutamate AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) GluA1 subunit and the GABA receptor (γ-Aminobutyric Acid) subtype GABAA α1 subunit in the hippocampus of the same animals.
RESULTS: We found no significant changes in locomotor activity (p > 0.05). The water T-maze data showed that 30 mg/kg dose significantly (p 0.05). Histological data revealed no neuronal morphological changes. Immunohistochemical analysis revealed increased expression of the AMPA GluA1 receptor subunit but there was no effect on GABAA receptor α1 subunit expression in the CA1 and CA2 subregions of the hippocampus.
CONCLUSIONS: The C. asiatica extract therefore improved hippocampus-dependent spatial learning and memory in a dose-dependent manner in rats through the GluA1-containing AMPA receptor in the CA1 and CA2 sub regions of the hippocampus.
RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.