ILIA STATE UNIVERSITY ONLINE PLATFORM FOR RESEARCH

Projects

    Ongoing
2021-12-31 - 2025-12-30

Impact of White Noise on Brain Pathophysiology and Neurotransmitter Release Machinery

Post-traumatic stress disorder or PTSD attributed to traumatic life experiences, explosions, or continuous loud white noise pollution, has been demonstrated to result in memory loss and anxiety, among other health detriments. PTSD is shattering the lives of thousands of soldiers returning from active duty and millions of individuals, especially in Low and Middle-Income Countries, exposed to PTSD-inducing high-amplitude white noise. At the nerve terminal, 15 nm cup-shaped lipoprotein structures called ‘porosomes’ composed of 40 proteins (as opposed to 120 nm nuclear pore complex composed of >500 protein molecules) mediate neurotransmitter release. Several porosome proteins have previously been reported to be implicated in neurotransmission and neurological disorders. Our recent studies report altered porosome morphology in the amygdale, inferior colliculus and medial geniculate of the brain following exposure to either hypokinetic stress or loud white noise, suggesting chemical and consequential functional alterations of porosomes, neurotransmitter release, and brain function. The proposed application will test this hypothesis in a rat model using both female and male animals to provide a molecular understanding of white noise-induced alterations in the porosome and its consequence on brain function. We propose the following Aims: (1) Determine how white noise impacts the porosome structure and chemical composition in the medial geniculate nucleus, basolateral amygdale, and the hippocampus of the brain; (2) How neurotransmitter release is affected in these brain regions; (3) How learning and memory is affected by white noise exposure. The proposed study will involve the exposure of 6-month-old female and male Wistar rats to different periods [1h/day for 5, 10 and 30 days] of white noise at varying amplitudes [10, 25 and 100 dB]. To determine changes in porosome structure, electron microscopy and expansion microscopy will be used; the chemistry of porosome main proteins will be detected using Western blotting; the function of porosome will be determined on isolated porosomes reconstituted on tissue slices and isolated synaptosomes, using EPC9 bilayer assays. To determine changes in learning, memory and emotional sphere following noise exposure, the multi-branch maze, Morris water maze, open field and elevated plus maze tasks will be utilized. Besides helping elucidate some of the molecular underpinnings of PTSD-inducing white noise on brain function and possible treatments, the study will contribute to the broader understanding of neurotransmission and brain function.


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