Impaired spatial navigation and age-dependent hippocampal synaptic dysfunction are associated with chronic...

Area of Science:

• Neuroscience
• Endocrinology
• Gerontology

Background:

• Type 2 diabetes mellitus (T2DM) is a known risk factor for Alzheimer's disease (AD).
• The specific impact of T2DM on hippocampal function and synaptic integrity during aging remains under-investigated.
• Neuroinflammation is a proposed mechanism linking T2DM and cognitive impairment in AD.

Purpose of the Study:

• To investigate the combined effects of aging and T2DM on AD-like pathology in the hippocampus.
• To assess cognitive function, neuronal integrity, synaptic markers, and neuroinflammation in a mouse model of T2DM.

Main Methods:

• Utilized leptin receptor-deficient db/db mice as a model for T2DM.
• Assessed spatial learning and memory using the Morris water maze (MWM).
• Conducted morphological analysis, measured synaptic protein expression (synaptophysin, PSD95), and analyzed cytokine profiles.

Main Results:

• T2DM mice exhibited impaired spatial acquisition and age-dependent neuronal loss in the dentate gyrus.
• Decreased astrocyte density and increased microglial activation were observed in the hippocampus of T2DM mice.
• Aged T2DM mice showed reduced expression of synaptic markers and elevated pro-inflammatory cytokines, indicating impaired synaptic integrity and exacerbated neuroinflammation.

Conclusions:

• T2DM impairs cognitive function through neuronal loss in the dentate gyrus.
• Aging exacerbates T2DM-induced hippocampal synaptic deterioration and neuroinflammation.
• These findings highlight the critical role of aging in T2DM's contribution to AD-like pathology.