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HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration

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Abstract

HIV infection and drugs of abuse induce oxidative stress and redox imbalance, which cause neurodegeneration. The mechanisms by which HIV infection and cocaine consumption affect astrocyte energy metabolism, and how this leads to neurodegenerative dysfunction, remain poorly understood. Presently, we investigated how oxidative injury causes the depletion of energy resources and glutathione synthetase (GSS), which in turn activates 5’ AMP-activated protein kinase (AMPK), glycolytic enzymes, and mitochondrial biogenesis, finally resulting in nuclear factor erythroid (NRF) transcription in astrocytes. Both human primary astrocytes incubated with HIV-1 Tat protein in vitro and HIV-inducible Tat (iTat) mice exposed to cocaine showed decreased levels of GSS and increased superoxide dismutase (SOD) levels. These changes, in turn, significantly activated AMPK and raised the concentrations of several glycolytic enzymes, along with oxidative phosphorylation, the mitochondrial biogenesis of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) and mitochondrial transcription factor (TFAM), and Nrf1 and Nrf2 gene transcription and protein expression. Moreover, neurons exposed to HIV-1Tat/cocaine-conditioned media showed reductions in dendritic formation, spine density, and neuroplasticity compared with control neurons. These results suggest that redox inhibition of GSS altered AMPK activation and mitochondrial biogenesis to influence Nrf transcription. These processes are important components of the astrocyte signaling network regulating brain energy metabolism in HIV-positive cocaine users. In conclusion, HIV-1 Tat alters redox inhibition, thus increasing glycolytic metabolic profiles and mitochondrial biogenesis, leading to Nrf transcription, and ultimately impacting astrocyte energy resource and metabolism. Cocaine exacerbated these effects, leading to a worsening of neurodegeneration.

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Abbreviations

iTat:

HIV-1 inducible Tat (transgenic mice)

HIV-1 Tat:

Transactivator protein

ROS:

Reactive oxygen species

GFAP:

Glial acidic fibril protein

GSS:

Glutathione synthetase

CAT:

Catalase

SOD:

Super oxide dismutase

HAND:

HIV-associated neurocognitive disorders

AMPK:

5′ AMP-activated protein kinase

HK:

Hexo kinase

ACC:

Acetyl coenzyme A

PFK:

Phosphofructokinase

LDHA:

Lactate dehydrogenase

MCT:

Monocarboxylate transporters

PGC1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

TFAM:

Transcription factor A, mitochondrial

CaMK:

Ca2+/calmodulin-dependent protein kinase

CREB:

cAMP response element-binding protein

ACC:

Acetyl-CoA carboxylase

OXPHOS:

Oxidative phosphorylation

NRF:

Nuclear respiratory factor

ARE:

Antioxidant response element

References

  1. Kaul M, Zheng J, Okamoto S, Gendelman HE, Lipton SA (2005) HIV-1 infection and AIDS: consequences for the central nervous system. Cell Death Differ 12:878–892. https://doi.org/10.1038/sj.cdd.4401623

    Article  CAS  PubMed  Google Scholar 

  2. Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202:13–23. https://doi.org/10.1016/s0022-510x(02)00207-1

    Article  CAS  PubMed  Google Scholar 

  3. Amarapal P, Tantivanich S, Balachandra K, Matsuo K, Pitisutithum P, Chongsa-nguan M (2005) The role of the TAT gene in the pathogenesis of HIV infection. Southeast Asian J Trop Med Public Health 36:352–361

    CAS  PubMed  Google Scholar 

  4. Sabatier JM, Mabrouk K, Vives E et al (1992) Evidence for neurotoxic activity of Tat from human immunodeficiency virus type 1. J Virol 65:961–996

    Article  Google Scholar 

  5. Peruzzi F (2006) The multiple functions of HIV-1 Tat: proliferation versus apoptosis. Front Biosci 11:708. https://doi.org/10.2741/1829

    Article  CAS  PubMed  Google Scholar 

  6. Chauhan A, Turchan J, Pocernich C, Bruce-Keller A, Roth S, Butterfield DA, Major EO, Nath A (2003) Intracellular human immunodeficiency virus Tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport. J Biol Chem 278:13512–13519. https://doi.org/10.1074/jbc.M209381200

    Article  CAS  PubMed  Google Scholar 

  7. Bartz SR, Emerman M (1999) Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8. J Virol 73:1956–1963

    Article  CAS  Google Scholar 

  8. De Simone FI, Darbinian N, Amini S et al (2016) HIV-1 Tat and cocaine impair survival of cultured primary neuronal cells via a mitochondrial pathway. J NeuroImmune Pharmacol 11:358–368. https://doi.org/10.1007/s11481-016-9669-6

    Article  PubMed  PubMed Central  Google Scholar 

  9. Badisa RB, Kumar SS, Mazzio E, Haughbrook RD, Allen JR, Davidson MW, Fitch-Pye CA, Goodman CB (2015) N-acetyl cysteine mitigates the acute effects of cocaine-induced toxicity in astroglia-like cells. PLoS One 10:e0114285. https://doi.org/10.1371/journal.pone.0114285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Narvaez JCM, Magalhães PV, Fries GR, Colpo GD, Czepielewski LS, Vianna P, Chies JAB, Rosa AR et al (2013) Peripheral toxicity in crack cocaine use disorders. Neurosci Lett 544:80–84. https://doi.org/10.1016/j.neulet.2013.03.045

    Article  CAS  PubMed  Google Scholar 

  11. Castilla-Ortega E, Ladrón de Guevara-Miranda D, Serrano A, Pavón FJ, Suárez J, Rodríguez de Fonseca F, Santín LJ (2017) The impact of cocaine on adult hippocampal neurogenesis: potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder. Biochem Pharmacol 141:100–117. https://doi.org/10.1016/j.bcp.2017.05.003

    Article  CAS  PubMed  Google Scholar 

  12. Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT (2002) Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 31:62–69. https://doi.org/10.1097/00126334-200210012-00006

    Article  Google Scholar 

  13. Samikkannu T, Rao KVK, Arias AY, Kalaichezian A, Sagar V, Yoo C, Nair MPN (2013) HIV infection and drugs of abuse: role of acute phase proteins. J Neuroinflammation 10:113. https://doi.org/10.1186/1742-2094-10-113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bélanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 4:724–738. https://doi.org/10.1016/j.cmet.2011.08.016

    Article  CAS  Google Scholar 

  15. Valcour V, Shiramizu B (2004) HIV-associated dementia, mitochondrial dysfunction, and oxidative stress. Mitochondrion 4:119–129. https://doi.org/10.1016/j.mito.2004.05.009

    Article  CAS  PubMed  Google Scholar 

  16. Chang E, Sekhar R, Patel S, Balasubramanyam A (2007) Dysregulated energy expenditure in HIV-infected patients: a mechanistic review. Clin Infect Dis 44:1509–1517. https://doi.org/10.1086/517501

    Article  PubMed  Google Scholar 

  17. Schweinsburg BC, Taylor MJ, Alhassoon OM, Gonzalez R, Brown GG, Ellis RJ, Letendre S, Videen JS et al (2005) Brain mitochondrial injury in human immunodeficiency virus-seropositive (HIV+) individuals taking nucleoside reverse transcriptase inhibitors. J Neuro-Oncol 11:356–364. https://doi.org/10.1080/13550280591002342

    Article  CAS  Google Scholar 

  18. Araque A (2006) Astrocyte-neuron signaling in the brain--implications for disease. Curr Opin Investig Drugs 7:619–624

    CAS  PubMed  Google Scholar 

  19. Sidoryk-Wegrzynowicz M, Wegrzynowicz M, Lee E, Bowman AB, Aschner M (2011) Role of astrocytes in brain function and disease. Toxicol Pathol 39:115–123. https://doi.org/10.1177/0192623310385254

    Article  PubMed  Google Scholar 

  20. Allaman I, Bélanger M, Magistretti PJ (2011) Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci 34:76–87. https://doi.org/10.1016/j.tins.2010.12.001

    Article  CAS  PubMed  Google Scholar 

  21. van der Knaap JA, Verrijzer CP (2016) Undercover: gene control by metabolites and metabolic enzymes. Genes Dev 30:2345–2369. https://doi.org/10.1101/gad.289140.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Forrester SJ, Kikuchi DS, Hernandes MS et al (2018) Reactive oxygen species in metabolic and inflammatory signaling. Circ Res 22:877–902

    Article  Google Scholar 

  23. Dringen R (2000) Metabolism and functions of glutathione in brain. Prog Neurobiol 62:649–671. https://doi.org/10.1016/s0301-0082(99)00060-x

    Article  CAS  PubMed  Google Scholar 

  24. Cobley JN (2018) Synapse pruning: mitochondrial ROS with their hands on the shears. BioEssays 40:1800031. https://doi.org/10.1002/bies.201800031

    Article  Google Scholar 

  25. Samikkannu T, Atluri VSR, Nair MPN (2016) HIV and cocaine impact glial metabolism: energy sensor AMP-activated protein kinase role in mitochondrial biogenesis and epigenetic remodeling. Sci Rep 6:31784. https://doi.org/10.1038/srep31784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Natarajaseenivasan K, Cotto B, Shanmughapriya S, Lombardi AA, Datta PK, Madesh M, Elrod JW, Khalili K et al (2018) Astrocytic metabolic switch is a novel etiology for cocaine and HIV-1 Tat-mediated neurotoxicity article. Cell Death Dis 9:415. https://doi.org/10.1038/s41419-018-0422-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Baum MK, Rafie C, Lai S, Sales S, Page B, Campa A (2009) Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users. J Acquir Immune Defic Syndr 50:93–99. https://doi.org/10.1097/QAI.0b013e3181900129

    Article  PubMed  Google Scholar 

  28. Cofrancesco J, Scherzer R, Tien PC et al (2008) Illicit drug use and HIV treatment outcomes in a US cohort. AIDS 22:357–365. https://doi.org/10.1097/QAD.0b013e3282f3cc21

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hee JK, Martemyanov KA, Thayer SA (2008) Human immunodeficiency virus protein Tat induces synapse loss via a reversible process that is distinct from cell death. J Neurosci 28:12604–12613. https://doi.org/10.1523/JNEUROSCI.2958-08.2008

    Article  CAS  Google Scholar 

  30. Paris JJ, Carey AN, Shay CF, Gomes SM, He JJ, McLaughlin JP (2014) Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice. Neuropsychopharmacology 39:380–388. https://doi.org/10.1038/npp.2013.201

    Article  CAS  PubMed  Google Scholar 

  31. Samikkannu T, Rao KVK, Pilakka Kanthikeel S, Subba Rao Atluri V, Agudelo M, Roy U, Nair MPN (2014) Immunoneuropathogenesis of HIV-1 clades B and C: role of redox expression and thiol modification. Free Radic Biol Med 69:136–144. https://doi.org/10.1016/j.freeradbiomed.2013.12.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Smith DL, Pozueta J, Gong B, Arancio O, Shelanski M (2009) Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proc Natl Acad Sci U S A 106:16877–16882. https://doi.org/10.1073/pnas.0908706106

    Article  PubMed  PubMed Central  Google Scholar 

  33. Samikkannu T, Agudelo M, Gandhi N, Reddy PVB, Saiyed ZM, Nwankwo D, Nair MPN (2011) Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: Implications for neuroAIDS. J Neuro-Oncol 17:230–238. https://doi.org/10.1007/s13365-011-0026-5

    Article  CAS  Google Scholar 

  34. Buch S, Yao H (2011) HIV-1 Tat toxin. In: Reproductive and developmental toxicology. Elsevier Inc, pp. 773–780

  35. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623. https://doi.org/10.1111/j.1471-4159.1992.tb10990.x

    Article  CAS  PubMed  Google Scholar 

  36. Dickens AM, Anthony DC, Deutsch R, Mielke MM, Claridge TDW, Grant I, Franklin D, Rosario D et al (2015) Cerebrospinal fluid metabolomics implicate bioenergetic adaptation as a neural mechanism regulating shifts in cognitive states of HIV-infected patients. AIDS 29:559–569. https://doi.org/10.1097/QAD.0000000000000580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cotto B, Natarajanseenivasan K, Langford D (2019) HIV-1 infection alters energy metabolism in the brain: contributions to HIV-associated neurocognitive disorders. Prog Neurobiol 181:101616. https://doi.org/10.1016/j.pneurobio.2019.101616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ratai EM, Annamalai L, Burdo T, Joo CG, Bombardier JP, Fell R, Hakimelahi R, He J et al (2011) Brain creatine elevation and N-acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of NeuroAIDS. Magn Reson Med 66:625–634. https://doi.org/10.1002/mrm.22821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N et al (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236:313–322. https://doi.org/10.1006/bbrc.1997.6943

    Article  CAS  PubMed  Google Scholar 

  40. Perfeito R, Cunha-Oliveira T, Rego AC (2013) Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease-resemblance to the effect of amphetamine drugs of abuse. Free Radic Biol Med 62:186–201. https://doi.org/10.1016/j.freeradbiomed.2013.05.042

    Article  CAS  PubMed  Google Scholar 

  41. Valente MJ, Carvalho F, Bastos ML et al (2012) Contribution of oxidative metabolism to cocaine-induced liver and kidney damage. Curr Med Chem 19:5601–5606. https://doi.org/10.2174/092986712803988938

    Article  CAS  PubMed  Google Scholar 

  42. Dutta R, Roy S (2012) Mechanism(s) involved in opioid drug abuse modulation of HAND. Curr HIV Res 10:469–477. https://doi.org/10.2174/157016212802138805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sen CK (1998) Glutathione: a key role in skeletal muscle metabolism. In: Oxidative stress in skeletal muscle. Birkhäuser, Basel, pp. 127–139

    Chapter  Google Scholar 

  44. Cacciatore I, Baldassarre L, Fornasari E, Mollica A, Pinnen F (2012) Recent advances in the treatment of neurodegenerative diseases based on GSH delivery systems. Oxidative Med Cell Longev 2012:240146–240112. https://doi.org/10.1155/2012/240146

    Article  CAS  Google Scholar 

  45. Pace GW, Leaf CD (1995) The role of oxidative stress in HIV disease. Free Radic Biol Med 19:523–528. https://doi.org/10.1016/0891-5849(95)00047-2

    Article  CAS  PubMed  Google Scholar 

  46. Walker J, Winhusen T, Storkson JM, Lewis D, Pariza MW, Somoza E, Somoza V (2014) Total antioxidant capacity is significantly lower in cocaine-dependent and methamphetamine-dependent patients relative to normal controls: results from a preliminary study. Hum Psychopharmacol 29:537–543. https://doi.org/10.1002/hup.2430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Thangavel S, Mulet CT, Atluri VSR, Agudelo M, Rosenberg R, Devieux JG, Nair MPN (2018) Oxidative stress in HIV infection and alcohol use: role of redox signals in modulation of lipid rafts and ATP-binding cassette transporters. Antioxid Redox Signal 28:324–337. https://doi.org/10.1089/ars.2016.6830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cardaci S, Ciriolo MR (2012) TCA cycle defects and cancer: when metabolism tunes redox state. Int J Cell Biol 2012:1–9

    Article  Google Scholar 

  49. Wu SB, Wu YT, Wu TP, Wei YH (2014) Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. Biochim Biophys Acta, Gen Subj 1840:1331–1344. https://doi.org/10.1016/j.bbagen.2013.10.034

    Article  CAS  Google Scholar 

  50. Buch S, Yao H, Guo M, Mori T, Mathias-Costa B, Singh V, Seth P, Wang J et al (2012) Cocaine and HIV-1 interplay in CNS: cellular and molecular mechanisms. Curr HIV Res 10:425–428. https://doi.org/10.2174/157016212802138823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fan Y, Gao X, Chen J, Liu Y, He JJ (2016) HIV Tat impairs neurogenesis through functioning as a notch ligand and activation of notch signaling pathway. J Neurosci 36:11362–11373. https://doi.org/10.1523/JNEUROSCI.1208-16.2016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Harris JJ, Jolivet R, Attwell D (2012) Synaptic energy use and supply. Neuron 75:762–777. https://doi.org/10.1016/j.neuron.2012.08.019

    Article  CAS  PubMed  Google Scholar 

  53. Rangaraju V, Calloway N, Ryan TA (2014) Activity-driven local ATP synthesis is required for synaptic function. Cell 156:825–835. https://doi.org/10.1016/j.cell.2013.12.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Pathak D, Shields LY, Mendelsohn BA, Haddad D, Lin W, Gerencser AA, Kim H, Brand MD et al (2015) The role of mitochondrially derived ATP in synaptic vesicle recycling. J Biol Chem 290:22325–22336. https://doi.org/10.1074/jbc.M115.656405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hardie DG (2011) AMP-activated protein kinase-an energy sensor that regulates all aspects of cell function. Genes Dev 25:1895–1908. https://doi.org/10.1101/gad.17420111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Valle-Casuso JC, Angin M, Volant S et al (2019) Cellular metabolism is a major determinant of HIV-1 reservoir seeding in CD4 + T cells and offers an opportunity to tackle infection. Cell Metab 29:611–626.e5. https://doi.org/10.1016/j.cmet.2018.11.015

    Article  CAS  PubMed  Google Scholar 

  57. Nederlof R, Eerbeek O, Hollmann MW, Southworth R, Zuurbier CJ (2014) Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart. Br J Pharmacol 171:2067–2079. https://doi.org/10.1111/bph.12363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Halestrap AP, Wilson MC (2012) The monocarboxylate transporter family-role and regulation. IUBMB Life 64:109–119. https://doi.org/10.1002/iub.572

    Article  CAS  PubMed  Google Scholar 

  59. Bergersen LH, Gjedde A (2012) Is lactate a volume transmitter of metabolic states of the brain? Front Neuroenerg 4:5. https://doi.org/10.3389/fnene.2012.00005

    Article  CAS  Google Scholar 

  60. Jäer S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc Natl Acad Sci U S A 104:12017–12022. https://doi.org/10.1073/pnas.0705070104

    Article  CAS  Google Scholar 

  61. Wang S, Sun H, Ma J, Zang C, Wang C, Wang J, Tang Q, Meyer CA et al (2013) Target analysis by integration of transcriptome and ChIP-seq data with BETA. Nat Protoc 8:2502–2515. https://doi.org/10.1038/nprot.2013.150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dinkova-Kostova AT, Abramov AY (2015) The emerging role of Nrf2 in mitochondrial function. Free Radic Biol Med 88:179–188. https://doi.org/10.1016/j.freeradbiomed.2015.04.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Virbasius JV, Scarpulla RC (1994) Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis. Proc Natl Acad Sci U S A 91:1309–1313. https://doi.org/10.1073/pnas.91.4.1309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS, Clayton DA (1998) Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18:231–236. https://doi.org/10.1038/ng0398-231

    Article  CAS  PubMed  Google Scholar 

  65. Rasbach KA, Schnellmann RG (2007) PGC-1α over-expression promotes recovery from mitochondrial dysfunction and cell injury. Biochem Biophys Res Commun 355:734–739. https://doi.org/10.1016/j.bbrc.2007.02.023

    Article  CAS  PubMed  Google Scholar 

  66. Rohas LM, St-Pierre J, Uldry M, Jager S, Handschin C, Spiegelman BM (2007) A fundamental system of cellular energy homeostasis regulated by PGC-1α. Proc Natl Acad Sci U S A 104:7933–7938. https://doi.org/10.1073/pnas.0702683104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Dirks B, Hanke J, Krieglstein J, Stock R, Wickop G (1980) Studies on the linkage of energy metabolism and neuronal activity in the isolated perfused rat brain. J Neurochem 35:311–317. https://doi.org/10.1111/j.1471-4159.1980.tb06266.x

    Article  CAS  PubMed  Google Scholar 

  68. Nabetani M, Okada Y, Kawai S, Nakamura H (1995) Neural activity and the levels of high energy phosphates during deprivation of oxygen and/or glucose in hippocampal slices of immature and adult rats. Int J Dev Neurosci 13:3–12. https://doi.org/10.1016/0736-5748(95)95839-V

    Article  CAS  PubMed  Google Scholar 

  69. Swinton MK, Carson A, Telese F, Sanchez AB, Soontornniyomkij B, Rad L, Batki I, Quintanilla B et al (2019) Mitochondrial biogenesis is altered in HIV+ brains exposed to ART: Implications for therapeutic targeting of astroglia. Neurobiol Dis 130:104502. https://doi.org/10.1016/j.nbd.2019.104502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Samikkannu T, Atluri VSR, Arias AY, Rao K, Mulet C, Jayant R, Nair M (2014) HIV-1 subtypes B and C Tat differentially impact synaptic plasticity expression and implicates HIV-associated neurocognitive disorders. Curr HIV Res 12:397–405. https://doi.org/10.2174/1570162x13666150121104720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Atluri VSR, Kanthikeel SP, Reddy PVB, Yndart A, Nair MPN (2013) Human synaptic plasticity gene expression profile and dendritic spine density changes in HIV-infected human CNS cells: role in HIV-associated neurocognitive disorders (HAND). PLoS One 8:e61399. https://doi.org/10.1371/journal.pone.0061399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

The present study was supported by a grant from the National Institutes of Health (NIH): R01DA 044872 to S. Thangavel.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, 1010 W Avenue B, Kingsville, TX, 78363, USA

    Kalaiselvi Sivalingam & Thangavel Samikkannu

  2. Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32611, USA

    Thomas J. Cirino & Jay P. McLaughlin

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  1. Kalaiselvi Sivalingam
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  4. Thangavel Samikkannu
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TS participated in the design of the study and wrote the paper; KS carried out the gene and protein experiments. TJC and JPM treated the mice and harvested tissue.

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Correspondence to Thangavel Samikkannu.

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The studies involving mice were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Florida, Gainesville, Florida, in accordance with the 2011 National Institute of Health Guide for the Care and Use of Laboratory Animals.

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Sivalingam, K., Cirino, T.J., McLaughlin, J.P. et al. HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration. Mol Neurobiol 58, 490–504 (2021). https://doi.org/10.1007/s12035-020-02131-w

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