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

Author:

Karimani Farnaz1,Taei Afsaneh Asgari1,Kaveh Neda1,Ghahfarokhi Mohammad Rabiei2,Abolghasemi-Dehaghani Mohammad-Reza2,Dargahi Leila1

Affiliation:

1. Shahid Beheshti University of Medical Sciences

2. University of Tehran

Abstract

Abstract

Alzheimer's disease is characterized by memory loss and pathological changes in the brain such as amyloid beta and tau pathology, as well as irregular neural network activity. We studied how intranasal insulin impacts memory and neural oscillations in an Alzheimer's disease rat model induced by STZ. Male Wistar rats were subjected to intracerebroventricular STZ injection, followed by intranasal insulin therapy. Electrophysiological recordings were conducted in the hippocampus and medial prefrontal cortex to assess local field potentials, elucidating insignificant alterations in theta-gamma oscillations following insulin treatment. However, insulin administration ameliorated deficits in hippocampal sharp-wave ripples and augmented hippocampal-prefrontal theta coherence. Concurrently, insulin therapy conferred enhancements in spatial memory and object recognition memory performance in behavioral tests. Furthermore, insulin mitigated tau protein pathology and hippocampal neuronal loss. Our findings underscore the potential of intranasal insulin to enhance memory function via modulating hippocampal-prefrontal cortical synchronization and alleviating impairments in hippocampal sharp-wave ripples.

Publisher

Research Square Platform LLC

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