Center for Molecular and Behaviorial Neuroscience
In order to gain a full understanding of common mental health and behavioral disorders we must understand both the molecular underpinnings of the problem as well as the social factors that contribute to it. The mission of the Center for Molecular and Behavioral Neuroscience is to conduct research in all phases—basic, translational, clinical, social, and behavioral—that will generate new knowledge and perhaps reduce health disparities in neurological disease and mental health.
Just two years into its development at Meharry, the Center is connecting independent researchers from various disciplines of study, allowing dynamic face-time for budding researchers in their rotations and summer internships. They are being exposed to cutting-edge research: the Center’s neuro-scientific approach is an advanced method for engaging in such work.
The Center for Molecular and Behavioral Neuroscience is an NIH R01 supported program.
The long term goal of our laboratory research is to identify, understand and eliminate factors responsible for the profoundly disproportionate burden of HIV/AIDS among minority populations in the United States. To achieve this goal our current laboratory research focuses on understanding the biochemical mechanisms of HIV-1 infection and pathogenesis. The specific projects currently being pursued in our laboratory are as follows:
1) Understanding the effects of cocaine on HIV-1 replication
Funding Source: National Institute on Drug Abuse/NIH
Project Summary: Cocaine is one of the commonly used drugs among HIV-infected patients. HIV positive patients who use cocaine have have a greater risk for AIDS-related death. However, underlying mechanism by which cocaine enhances HIV-1 replication remains unknown. In this project we are examining the mechanism by which cocaine enhances HIV-1 replication in primary CD4+ T cells.
2) Examining the synergistc effects of cocaine and HIV-1 on CD4+ T cell decline
Funding Source: Vanderbilt CTSA
Project Summary: CD4+ T cell loss is an important indicator of HIV-1 disease progression. Clinical studies suggest that cocaine abuse accelerates CD4+ T cell loss in HIV-1 infected patients. This research project focuses on examining the synergy between cocaine and HIV-1 virions on CD4+ T cell death in an ex vivo model.
3) Determining the effects of methamphetamine on HIV-1 infection/replication
Funding Source: National Institute on Drug Abuse/NIH
Project Summary: Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. However, a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in human patients. Therefore, the goal of this project is to test the effects of methamphetamine on HIV-1 replication in CD4+ T cells that are the primary targets of HIV in vivo.
4) Examining a direct and functional role of HIV-1 capsid on viral DNA integration
Funding Source: Pittsburgh Center for HIV Protein Interaction, Univ. of Pittsburgh
Project Summary: HIV-1 capsid (CA) is a multifunctional viral protein that plays important roles in reverse transcription and nuclear import of the pre-integration complex (PIC). Despite significant advances in recent years on HIV-1 CA structure and function, a key knowledge gap in the early stages of HIV-1 infection is the potential role of CA in viral DNA integration. The goal of this project is to understand the biochemical basis underlying the role of HIV-1 capsid (CA) in viral integration.
Clivel George Charlton, Ph.D.
Department of Neurobiology and Neurotoxicology
Dr. Charlton’s laboratory is exploring the possible causal relationship between excess methylation in the brain and Parkinson’s disease. Methylation depletes the amount of the essential neurotransmitter dopamine and increases levels of lyso-phosphatidyl choline, which disrupts the structure of biological membranes in the microcompartment where this occurs. Dr. Charlton and his colleagues have observed that injection of the methyl donor, S-adenosyl-methionine (SAM), into the brain of rodents results in extensive brain methylation and causes transient tremor, hypokinesia, rigidity, and abnormal posture, changes that resemble the motor deterioration that accompanies Parkinson’s. Consistent with their hypothesis of a role of methylation in the pathway leading to Parkinson’s disease is the finding that MPP+, a toxic metabolite linked to Parkinson’s disease development in human beings, increases SAM-dependent methylation in the brain. The laboratory is exploring possible therapeutic interventions to alter these methylation processes. Interestingly, a current Parkinson’s therapy, L-dopa, diminishes the Parkinson’s-like symptoms in SAM-injected rats. However, there are considerable side effects and loss of effects of L-dopa when given therapeutically. Dr. Charlton and his colleagues are also exploring the molecular basis for these unwanted treatment sequelae.
Sukhbir Mokha, Ph.D.
Professor, Meharry Department of Neuroscience and Pharmacology
Adjunct Professor of Pharmacology, Vanderbilt University
Director of Graduate Studies, Neuroscience Program
Dr. Mokha’s laboratory is investigating the neurobiology of pain and analgesia in normal and pathological states using electrophysiological, behavioral, cellular, and molecular techniques. Many painful syndromes/disorders such as migraine, trigeminal neuralgia, temporomandibular joint disorder (TMJ/TMD), and irritable bowel syndrome (IBS) are more prevalent in women than in men. Dr. Mokha and his colleagues are interested in understanding the biological mechanisms that generate the higher prevalence of painful syndromes in women. Specifically, the laboratory is investigating whether activation of endogenous noradrenergic or serotonergic pathways involving G protein–coupled receptors (opioid, noradrenergic, and serotonergic) produce estrogen-dependent, sex-specific inhibition of pain mechanisms , in both spinal and trigeminal systems. Estrogen-dependent decreased inhibition in the female could contribute to the higher prevalence of painful syndromes in women. They have already provided evidence that estrogen decreases the analgesic effects produced by activation of α₂-adrenoceptors and opiod or opiod-like receptors (ORL1) in the spinal cord and trigeminal system and have shown that estrogen alters the expression of the gene encoding ORL1.
Models of Risk for PTSD
Matthew Morris, Ph.D.
National Institute of Child Health/Human Dev. (NICHD)
This project seeks to identify cognitive and neurobiological markers of risk for posttraumatic stress disorder (PTSD) and/or major depressive disorder (MDD) in the acute aftermath of trauma. The study will investigate longitudinal pathways leading from interpersonal violence (IPV) exposure to PTSD and/or MDD in a sample of 60 women recently exposed to IPV and 40 non-exposed women using four waves of data collection (within one month after exposure to IPV, and at one, three, and six months following the initial assessment). Although women are twice as likely as men to develop PTSD and/or MDD after exposure to trauma, the mechanisms underlying this increased risk remain unclear. Identifying individuals at elevated risk for these disorders is critical for developing effective early intervention programs.
Twum Ansah, Ph.D.
Department of Neuroscience and Pharmacology
The research in Dr. Twum Ansah’s laboratory seeks to understand the neurobiological mechanisms that mediate neurological disorders, such as Parkinson’s Disease as well as psychiatric disorders such as depression and drug abuse, all of which involve the dopaminergic system and its regulation by other systems, such as the serotonergic system. His major research efforts are being devoted to systematically investigate alterations in the serotonergic system and to understand its role in the hypokinesia produced by lesioning of the dopaminergic system with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The objective is to understand the role of serotonin in the neurobiology of Parkinson’s Disease and how manipulating the serotonergic system might alter the course of the disease, as a prelude to identification of novel therapeutic targets for the disease.
Mitchell Parks, M.D.
Assistant Professor, Department of Psychiatry & Behavioral Sciences
Dr. Parks’s research examines the nexus of two health disparities in African-American women: their documented increased incidence of alcohol use disorders and their prevalence of HIV infection. The technique employed to address the question of why these two disparities occur in this population is functional magnetic resonance imaging (fMRI). fMRI utilizes hemoglobin as a natural tracer to differentially determine activity in brain areas. Dr. Parks’s previous work with chronic alcoholic patients determined their different utilization of frontal and parietal regions in response to simple motor tasks. The objective in the work with African-American women is to use fMRI to determine whether routine or binge ingestion of alcohol incurs changes in brain physiology that might lead to HIV infection risk.