| 1. |
- Joseph, S. B., et al.
(författare)
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Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology
- 2023
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 227:SUPP1
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Tidskriftsartikel (refereegranskat)abstract
- Despite viral suppression with antiretroviral therapy (ART), people with human immunodeficiency virus (HIV) continue to experience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health disorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis and heterogeneity of mechanisms likely underlying CNS complications must be addressed in the development of preventive interventions and effective treatments. The biotyping approach has previously been useful to define phenotypes of other CNS diseases based on underlying mechanisms and could be translated to the field of neuroHIV. The purpose of the Biotype Workshop series, and the Virology, Immunology and Neuropathology Working Group in particular, is to capitalize on current and new technologies and guide future research efforts using the wealth of available immunological, virologic, and neuropathological data collected from people with HIV on and off ART.
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| 2. |
- Jacobs, M M, et al.
(författare)
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Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels
- 2013
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 18:11, s. 1205-1210
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Tidskriftsartikel (refereegranskat)abstract
- Opioid drugs are highly addictive and their abuse has a strong genetic load. Dopamine-glutamate interactions are hypothesized to be important for regulating neural systems central for addiction vulnerability. Balanced dopamine-glutamate interaction is mediated through several functional associations, including a physical link between discs, large homolog 4 (Drosophila) (DLG4, PSD-95) and dopamine receptor 1 (DRD1) within the postsynaptic density to regulate DRD1 trafficking. To address whether genetic associations with heroin abuse exist in relation to dopamine and glutamate and their potential interactions, we evaluated single-nucleotide polymorphisms of key genes within these systems in three populations of opiate abusers and controls, totaling 489 individuals from Europe and the United States. Despite significant differences in racial makeup of the separate samples, polymorphisms of DRD1 and DLG4 were found to be associated with opiate abuse. In addition, a strong gene-gene interaction between homer 1 homolog (Drosophila) (HOMER1) and DRD1 was predicted to occur in Caucasian subjects. This interaction was further analyzed by evaluating DRD1 genotype in relation to HOMER1b/c protein expression in postmortem tissue from a subset of Caucasian subjects. DRD1 rs265973 genotype correlated with HOMER1b/c levels in the striatum, but not cortex or amygdala; the correlation was inversed in opiate abusers as compared with controls. Cumulatively, these results support the hypothesis that there may be significant, genetically influenced interactions between glutamatergic and dopaminergic pathways in opiate abusers.
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