AdipoRon as a potential physical exercise-mimetic to ameliorate diabetes-associated cognitive impairment

Abstract

Dementia is a devastating neurodegenerative disease that is comorbid with other disabling maladies such as diabetes mellitus. Current theory posits that Alzheimer’s disease is the Type 3 diabetes since insulin signalling underlies the pathogenesis of diabetes and dementia. AdipoRon is an agonist of adiponectin receptors. It possesses anti-diabetic property by promoting insulin sensitisation. Its effects on counteracting diabetes-associated neurodegeneration and cognitive impairment have yet to be explored. The present study aims to investigate whether AdipoRon exerts pro-cognitive and neurotrophic effects on diabetic mouse model induced by streptozotocin. Intraperitoneal administration with 20 mg/kg AdipoRon continuously for 14 days restored adult neurogenesis, including cell proliferation, neuronal differentiation, as well as increased granule cell dendritic arborization and spine density in the dentate of diabetic animals. AdipoRon treatment also improved spatial memory in diabetic mice. Besides, acute bath application with 0.5 μM AdipoRon restored deficit in NMDA receptor-dependent synaptic plasticity at the medial perforant path in brain slices prepared from the diabetic animals. Lastly, AdipoRon treatment activated metabolic regulators, including AMPK and PGC-1α, as well as upregulated downstream BDNF levels. In summary, the present data demonstrated that AdipoRon could be a potential treatment for promoting diabetes-associated with cognitive impairment by promoting hippocampal neural plasticity via AMPK/PGC-1α/BDNF signalling pathway.