Led by Dr. Palsamy Periyasamy
University of Nebraska Medical Center
Study Overview:
Cocaine abuse poses a significant nationwide concern, impacting the United States, with rising instances in Nebraska. This addiction inflicts severe harm, particularly on the brain, with no existing treatment for mitigating cocaine-induced microglial activation, neuroinflammation, and resultant behavioral changes. Our pilot grant proposal seeks to explore the therapeutic potential of N-Acetylcysteine (NAC) as a target. We hypothesize that NAC can ameliorate cocaine-triggered mitochondrial stress, mito-lysosomal dysfunction, impaired mitophagy, and microglial activation through two key objectives. The first objective involves assessing NAC's therapeutic potential in countering cocaine-induced microglial activation and neuroinflammation in vitro, while the second objective aims to validate NAC's efficacy in mitigating cocaine-induced microglial activation, neuroinflammation, and behavioral alterations in vivo. This study holds promise for targeted therapeutics to mitigate cocaine-related neuroinflammation and behavioral consequences, with potential implications for other neurodegenerative conditions characterized by neuroinflammation.
Specific Aims:
The central hypothesis of this proposal is that NAC administration can alleviate cocaine-induced mitochondrial stress, mito-lysosomal dysfunction, impaired mitophagy, and microglial activation, ultimately ameliorating cocaine-induced neuroinflammation and associated behavioral changes. We will test this hypothesis through two specific aims.
(Aim 1): Determine the therapeutic potential of NAC in alleviating cocaine-mediated microglial activation and neuroinflammation in vitro.
(Aim 2): Validate the therapeutic efficacy of NAC in alleviating cocaine-induced microglial activation, neuroinflammation, and behavioral changes in vivo.
Study Sample Population:
N=15 (pregnant C57BI/6 wild-type mouse dams - and their newborn pups); N=96 (C57BL/6 wild-type mouse, 8-weeks-old).
Long-Term Goals:
The long-term goal of this project is to explore various adjunctive therapies for mitigating the neuroinflammatory and behavioral consequences of drug abuse. By delving into this potential, we aim to expand the available treatment options for drug addiction and associated neuroinflammation, ultimately contributing to better outcomes and improved quality of life for individuals affected by these conditions.
Dr. Palsamy Periyasamy
Project Director
Dr. Palsamy Periyasamy is an Assistant Professor in the Department of Pharmacology and Experimental Neuroscience, UNMC, specializing in epigenetic research. His work delves into the intricate realm of HIV-1, substance abuse, and their impact on neuroinflammation. By deciphering the epigenetic landscape, particularly focusing on promoter DNA methylation and non-coding RNAs, Dr. Periyasamy aims to uncover the underlying mechanisms that activate microglia and astrocytes, contributing to NeuroHIV. These investigations encompass various substances, including cocaine, morphine, methamphetamine, and alcohol. The knowledge gained from this research holds promise for innovative therapeutic strategies, addressing the challenges of HIV-associated neurocognitive disorders in the era of combined antiretroviral therapy.