UP-REGULATION OF SYNAPTOBREVIN-2 TO DELAY AGE-RELATED COGNITIVE IMPAIRMENT

Area of Science:

• Neuroscience
• Aging Research
• Molecular Biology

Background:

• Cognitive decline with age is characterized by slowed executive function and memory impairment.
• Expression levels of Vesicle Associated Membrane Protein 2 (VAMP2), also known as Synaptobrevin-2 (syb2), decrease with advancing age.
• The precise mechanisms driving age-related cognitive deficits remain largely unknown.

Purpose of the Study:

• To investigate the impact of overexpressing syb2 on cognitive function and synaptic plasticity in an aging mouse model.
• To determine if maintaining syb2 levels can counteract age-related memory impairment and synaptic dysfunction.

Main Methods:

• Development of a novel transgenic mouse model (TgV2) overexpressing syb2.
• Performance assessment of aged TgV2 mice and wild-type (WT) controls in spatial memory tests.
• Electrophysiological analysis of long-term potentiation (LTP) in hippocampal CA1 synapses.

Main Results:

• Aged TgV2 mice exhibited enhanced performance in spatial memory tests compared to age-matched WT controls.
• WT mice showed a significant reduction in syb2 levels with age, while TgV2 mice maintained normal levels.
• Increased long-term potentiation (LTP) was observed in hippocampal CA1 synapses of aged TgV2 mice.
• The beneficial effects on synaptic plasticity were observed in both male and female mice.

Conclusions:

• Overexpression of syb2 supports cognitive function throughout the aging process.
• Maintaining syb2 levels can mitigate age-related synaptic dysfunction and potentially delay dementia.
• VAMP2/syb2 represents a promising therapeutic target for combating age-related cognitive decline.