Progressive Degeneration and Adaptive Excitability in Dopamine D1 and D2 Receptor-Expressing Striatal Neurons Exposed to HIV-1 Tat and Morphine.

Autor: Lark ARS; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Silva LK; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA.; PPD®, Part of Thermo Fisher Scientific, Richmond, VA, 23230-3323, USA., Nass SR; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Marone MG; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Ohene-Nyako M; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Ihrig TM; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Marks WD; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA.; Department of Psychiatry, Southwestern Medical Center, University of Texas, Dallas, TX, 75235, USA., Yarotskyy V; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA., Rory McQuiston A; Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298-0709, USA., Knapp PE; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA.; Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298-0709, USA.; Institute for Drug and Alcohol Studies, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA., Hauser KF; Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Molecular Medicine Research Building, Room 4040, 1220 East Broad Street, PO Box 980613, Richmond, VA, 23298-0613, USA. kurt.hauser@vcuhealth.org.; Department of Anatomy and Neurobiology, School of Medicine, Virginia Commonwealth University, PO Box 980709, Richmond, VA, 23298-0709, USA. kurt.hauser@vcuhealth.org.; Institute for Drug and Alcohol Studies, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA. kurt.hauser@vcuhealth.org.
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2023 Apr; Vol. 43 (3), pp. 1105-1127. Date of Electronic Publication: 2022 Jun 13.
DOI: 10.1007/s10571-022-01232-5
Abstrakt: The striatum is especially vulnerable to HIV-1 infection, with medium spiny neurons (MSNs) exhibiting marked synaptodendritic damage that can be exacerbated by opioid use disorder. Despite known structural defects in MSNs co-exposed to HIV-1 Tat and opioids, the pathophysiological sequelae of sustained HIV-1 exposure and acute comorbid effects of opioids on dopamine D1 and D2 receptor-expressing (D1 and D2) MSNs are unknown. To address this question, Drd1-tdTomato- or Drd2-eGFP-expressing reporter and conditional HIV-1 Tat transgenic mice were interbred. MSNs in ex vivo slices from male mice were assessed by whole-cell patch-clamp electrophysiology and filled with biocytin to explore the functional and structural effects of progressive Tat and acute morphine exposure. Although the excitability of both D1 and D2 MSNs increased following 48 h of Tat exposure, D1 MSN firing rates decreased below control (Tat-) levels following 2 weeks and 1 month of Tat exposure but returned to control levels after 2 months. D2 neurons continued to display Tat-dependent increases in excitability at 2 weeks, but also returned to control levels following 1 and 2 months of Tat induction. Acute morphine exposure increased D1 MSN excitability irrespective of the duration of Tat exposure, while D2 MSNs were variably affected. That D1 and D2 MSN excitability would return to control levels was unexpected since both subpopulations displayed significant synaptodendritic degeneration and pathologic phospho-tau-Thr205 accumulation following 2 months of Tat induction. Thus, despite frank morphologic damage, D1 and D2 MSNs uniquely adapt to sustained Tat and acute morphine insults.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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