Hippocampal sharp-wave ripples and hippocampal-prefrontal synchrony regulate memory-enhancing effects of intranasal insulin in an STZ-induced Alzheimer's model

Abstract

Aims

Alzheimer's disease is characterized by memory loss and pathological changes in the brain, such as amyloid beta and tau pathology, disruptions in neural circuits and neuronal oscillations are also significant indicators of this disease and potential therapeutic targets. We studied how intranasal insulin impacts memory and neural oscillations in an Alzheimer's disease rat model induced by STZ.

Main methods

Male Wistar rats were intracerebroventricularly injected with STZ, followed by intranasal insulin therapy. Electrophysiological recordings were conducted in the hippocampus and medial prefrontal cortex to assess local field potentials. Memory was assessed using novel object recognition and Y-maze tests. Amyloid and tau pathology and neuronal loss were also evaluated in the hippocampus.

Key finding

Alterations in theta-gamma oscillations following insulin treatment were not significant. However, insulin administration ameliorated hippocampal sharp-wave ripples deficit and augmented hippocampal-prefrontal theta coherence. Concurrently, insulin therapy enhanced spatial memory and object recognition memory performance in behavioral tests. Insulin mitigated tau and amyloid pathology and hippocampal neuronal loss.

Significance

Our findings underscore the potential of intranasal insulin to enhance memory function by modulating hippocampal-prefrontal cortical synchronization and alleviating impairments in hippocampal sharp-wave ripples.