Determining the Localization of MOSCs in the Brain

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Methamphetamine (METH) is a highly addictive psychostimulant with destructive and potentially deadly consequences due to the excessive release of dopamine (DA), serotonin (5HT) and other biogenic amines. There is no FDA approved pharmacological treatment for METH abuse/overdose. Metal-Organic Super Containers (MOSCs) are a newly discovered class of synthetic supercontainers with endo- and Exo- cavities. These structures have features that can be manipulated to allow specific molecules to bind to them. MOSCs can sequester the molecules that are bound to their cavities, reducing the interaction with the outside environment. Prior research has determined the binding efficiency of MOSCs to 5HT and DA. We hypothesize that MOSCs will provide therapeutic value in reducing acute toxicity by binding transmitters that contribute to the neurotoxic cascade and long-term effects of METH. In exploratory studies, male Sprague-Dawley rats (300-400 grams) were used to assess MOSCs therapeutic potential in reducing METH-induced toxicity. Our initial findings indicate that following a neurotoxic exposure to METH, rats had higher DA content in the MOSC infused striatum when compared to the vehicle control infused striatum, indicating the ability of MOSCs to attenuate of the neurotoxic consequences of METH. In the most recent MOSC study, immunohistochemistry was used to explore the distribution of MOSCs in the brain. Results has shown that MOSCs can travel to the contralateral side of the striatum. We are not sure how this transport is occurring. Additionally, the MOSCs localized in the glial cells. In the future, a dose-response curve will be performed which can be used in combination with data relating to the distribution of the MOSCs to determine optimal dosage to maximize therapeutic effects.

First Advisor

Lisa McFadden

Second Advisor

Zhenqiang Wang

Research Area

Basic Biomedical Science

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