Ultrastructural Synaptic Differences in the Central Inferior Colliculus in the 3xTG Mouse Across Three Disease Stages

Area of Science:

• Neuroscience
• Auditory Neuroscience
• Alzheimer's Disease Research

Background:

• Hearing loss is a modifiable risk factor for Alzheimer's disease (AD).
• The inferior colliculus (IC), an auditory midbrain nucleus, experiences age-related changes impacting neurotransmission.
• Recent findings suggest the IC is involved in AD-related processing changes.

Purpose of the Study:

• To investigate synaptic ultrastructure changes in the central inferior colliculus (ICc) during the progression of Alzheimer's disease (AD) in a mouse model.
• To identify potential early synaptic biomarkers for AD in the ICc.

Main Methods:

• Transmission electron microscopy (EM) was employed to analyze synaptic ultrastructure in the ICc of 3xTG mice.
• Synapses were characterized by presynaptic vesicles, synaptic cleft, and postsynaptic density (symmetric vs. asymmetric).
• Quantification included presynaptic profile areas, active zone lengths, and presynaptic mitochondria.

Main Results:

• A significant reduction in both symmetric and asymmetric synapses was observed during the emerging AD stage.
• The density of symmetric synapses in the ICc decreased by approximately 50%.
• This loss occurred before the established disease stages, suggesting an early pathological event.

Conclusions:

• The substantial loss of symmetric synapses, which release inhibitory neurotransmitters like GABA, may contribute to central gain and hearing impairment (presbycusis) in AD.
• Alterations in the ICc's synaptic structure represent a potential early biomarker for Alzheimer's disease progression.
• These findings highlight the IC as a critical region for understanding AD's impact on auditory processing and cognition.