LSUHSC CARC Research Component 3: Alcohol Use Disorder & Associated Neurological Symptoms of Cognitive Dysfunction and Pain Alcohol use disorder (AUD) is characterized by neurological deficits, negative affective states, and a profound escalation of drinking. The cognitive and behavioral deficits associated with excessive drinking are attributed to functional and persistent changes to neuronal circuitry. Chronic alcohol induced-cognitive impairments are associated with selective central nervous system damage in areas such as the prefrontal cortex (PFC). Excessive alcohol exposure also damages the peripheral nervous system to produce a characteristic neuropathy, and the resulting hyperalgesia (increased pain sensitivity) is hypothesized to potentiate negative reinforcement processes to increase motivation for alcohol. Alcohol use also represents a major exacerbating factor for human immunodeficiency virus (HIV) disease. Even in the post-antiretroviral therapy (ART) era neurocognitive deficits remain prevalent in persons living with HIV (PLWH). HIV-associated neurocognitive disorder (HAND) and co-occurring AUD can exacerbate these deficits. PLWH also suffer from chronic pain, which disrupts physical and emotional function, interferes with ART adherence, and doubles the chance of virologic failure. Pain symptoms in PLWH are associated with specific changes in the brain and correspondingly associates with numerous psychosocial factors in this population, including depression. While cognitive deficits and pain are closely linked in PLWH, few studies have examined the stress-related neurobiological factors that drive these interactions or how alcohol and HIV promote this process. The PFC represents and executes the highest forms of goal-directed behavior, and its function is compromised in motivational disorders such as AUD. As a potential neurobiological correlate of pain and cognitive impairment in PLWH, preclinical studies from our group and others have implicated a functional potentiation of glucocorticoid receptor (GR) signaling in association with excessive alcohol drinking, cognitive dysfunction, and chronic pain. Heightened GR signaling and altered excitability of vulnerable cognition- and pain-related brain areas such as the PFC may thus represent a unifying mechanism contributing to these pathologies. Finally, emerging evidence suggests that Western diets commonly consumed in the United States worsen both neurocognitive and pain symptomatology. Thus, the neurobiological interaction of excessive alcohol drinking, cognition, and pain in the context of Western diet consumption represents a critically underexplored area of HIV research in the public interest. Our overarching hypothesis is that excessive drinking and HIV/ART exposure in individuals consuming a Western diet additively produce cognitive deficits and hyperalgesia in PLWH in association with increased glucocorticoid signaling and hyperexcitability within the PFC. We will examine these factors using a bidirectional translational experimental design incorporating human and nonhuman primate models.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Comprehensive Center (P60)
Project #
5P60AA009803-28
Application #
10075865
Study Section
Special Emphasis Panel (ZAA1)
Project Start
Project End
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
28
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Louisiana State Univ Hsc New Orleans
Department
Type
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Samuelson, Derrick R; Burnham, Ellen L; Maffei, Vincent J et al. (2018) The respiratory tract microbial biogeography in alcohol use disorder. Am J Physiol Lung Cell Mol Physiol 314:L107-L117
Glick, Jennifer L; Theall, Katherine P; Andrinopoulos, Katherine M et al. (2018) The Role of Discrimination in Care Postponement Among Trans-Feminine Individuals in the U.S. National Transgender Discrimination Survey. LGBT Health 5:171-179
Molina, Patricia E; Nelson, Steve (2018) Binge Drinking's Effects on the Body. Alcohol Res 39:99-109
Molina, Patricia E; Simon, Liz; Amedee, Angela M et al. (2018) Impact of Alcohol on HIV Disease Pathogenesis, Comorbidities and Aging: Integrating Preclinical and Clinical Findings. Alcohol Alcohol 53:439-447
Ford Jr, Stephen M; Simon Peter, Liz; Berner, Paul et al. (2018) Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques. Am J Physiol Endocrinol Metab :
Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela et al. (2018) Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting. Alcohol 66:35-43
Glick, Jennifer L; Andrinopoulos, Katherine M; Theall, Katherine P et al. (2018) ""Tiptoeing Around the System"": Alternative Healthcare Navigation Among Gender Minorities in New Orleans. Transgend Health 3:118-126
Glick, Jennifer L; Theall, Katherine; Andrinopoulos, Katherine et al. (2018) For data's sake: dilemmas in the measurement of gender minorities. Cult Health Sex :1-16
Theall, Katherine P; Felker-Kantor, Erica; Wallace, Maeve et al. (2018) Considering high alcohol and violence neighborhood context using daily diaries and GPS: A pilot study among people living with HIV. Drug Alcohol Depend 187:236-241
Simon, Liz; Siggins, Robert; Winsauer, Peter et al. (2018) Simian Immunodeficiency Virus Infection Increases Blood Ethanol Concentration Duration After Both Acute and Chronic Administration. AIDS Res Hum Retroviruses 34:178-184

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