Sexual dimorphism, altered hippocampal glutamatergic neurotransmission, and cognitive impairment in APP knock-in mice

Elevated stimulus-evoked glutamate release in young male APP mice declined with age compared to age-matched control mice.

• Young male APP mice showed increased glutamate release in the dentate gyrus and CA3 regions of the hippocampus.
• Young female APP mice demonstrated enhanced glutamate clearance in the CA1 region, which decreased with age.
• Both male and female APP mice exhibited reduced basal glutamate levels in the CA1, with males also experiencing depletion in the CA3.
• Aged male and female APP mice displayed impaired spatial cognition, while only aged females had recognition memory deficits.
• Findings indicate a sex-dependent change in glutamatergic signaling and suggest that female APP mice may experience a more severe cognitive decline.

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