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P3‐046: INSULIN RESISTANCE AND OBESITY IN CHILDHOOD AND LONG‐TERM CONSEQUENCES DURING AGING
Author(s) -
Pasinetti Giulio Maria
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.1133
Subject(s) - insulin resistance , hyperinsulinemia , endocrinology , obesity , medicine , insulin , overweight , morris water navigation task , hippocampal formation
the health care system. Vascular cognitive impairment, Alzheimer’s and other neurodegenerative diseases affect millions of elderly patients in the USA. According to recent results of the dementia research field a key event in the pathomechanism of dementia is the disruption of synaptic connections among neurons. Synapses are the structural elements for information processing, neuronal communication in the brain and essential for learning and memory as well as other cognitive processes. The core mechanism for transmitter release from synaptic vesicles requires the SNARE (SNAP Receptor) complex. Three proteins form the synaptic SNARE complex in the brain: SNAP-25, syntaxin1 and synaptobrevin. Methods: We used the synaptobrevin2 knock-out mouse strain as a novel model of dementia in the elderly as tested for spatial learning performance in the IntelliCage a novel automated assay environment; and fluorescence imaging assays of synaptic function on cultured neurons. Results: We have found that the levels of synaptobrevin2, a SNARE protein significantly declines with age. Synaptobrevin levels correlate with the rate of synaptic release. Interestingly, synaptic protein levels were also a good indicator of spatial learning performance in the reversal learning test using a novel automated assay environment. Conclusions: Although neuronal SNAREs are involved most specifically in the exocytosis of synaptic vesicles, we propose that their direct synaptic effects on multiple steps of vesicle mobilization includes synaptobrevin’s role in endocytosis as part of learning and memory in the etiology of Alzheimer’s disease. Based on these new results, we propose the SNARE driven vesicle recycling pathway as a possible therapeutic target and a novel approach to improve cognitive function in the patients suffering from Alzheimer’s disease.