Low socio-economic background, unemployment and depressed environmental surroundings play significant roles in outlook and behavior. Likewise, some individuals suffering from mood disorders may delay seeking healthcare or may not have healthcare benefits and turn to substance abuse (SA) as an alternative. Some comorbidities associated with SA and/or HIV infection directly affect behavior and cognition, and impact significantly on quality of life, adherence to anti-retroviral therapy and successful drug addiction treatment programs. In this context, alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Our broad hypothesis is that SA and HIV CNS disease contribute to disruptions in the hypothalamic pituitary thyroid (HPT) feedback loop and may lead to or exacerbate hypothyroidism. We propose that these disruptions occur, in part, at the level of hypothalamic signaling and may contribute, in part, to HPT syndrome observed in many individuals who abuse cocaine and are HIV positive. Results from our proposed exploratory study will provide valuable information needed to design more detailed studies addressing: molecular interactions among cocaine, HIV, HAART and CNS HPT signaling impact on cognitive dysfunction, behavior and disease progression treatment strategies for HIV patients with SA disorder at risk for thyroid disease. Our studies are designed to address if cocaine and/or HIV affect pre-existing subclinical or overt hypothyroidism to provide increased awareness among healthcare providers treating substance abuser and/or HIV patients. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Results from the proposed studies will increase our understanding of how altered hypothalamic signaling in patients suffering from SA disorders and/or HIV infection may contribute to declining cognition and disease progression, and/or treatment failure.
Alterations in thyroid hormone levels have emerged as a complication among some individuals with SA disorders and/or HIV infection, although the molecular basis for the connection is unknown. Left unchecked, the combination of these disorders could lead to increased SA and more rapid disease progression. Our study will provide information to address molecular interactions among cocaine, HIV, and CNS thyroid signaling.
| Kovalevich, Jane; Yen, William; Ozdemir, Ahmet et al. (2015) Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-? via a TNF-?/JNK- mediated mechanism. J Neuroimmune Pharmacol 10:55-73 |
| Kovalevich, Jane; Corley, Gladys; Yen, William et al. (2012) Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling. J Neurochem 121:302-13 |
| Kovalevich, Jane; Langford, Dianne (2012) Neuronal toxicity in HIV CNS disease. Future Virol 7:687-698 |
| Kovalevich, Jane; Corley, Gladys; Yen, William et al. (2012) Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a ?-lactam antibiotic during cocaine withdrawal. Am J Pathol 181:1921-7 |
| Langford, Dianne; Baron, David; Joy, Javed et al. (2011) Contributions of HIV infection in the hypothalamus and substance abuse/use to HPT dysregulation. Psychoneuroendocrinology 36:710-9 |
