Skip to main content

Advertisement

SpringerLink
Log in

Friends Turn Foe—Astrocytes Contribute to Neuronal Damage in NeuroAIDS

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Astrocytes play a wide variety of roles in the central nervous system (CNS). Various facets of astrocyte-neuron interplay, investigated for the past few decades, have placed these most abundant and important glial cell types to be of supreme importance for the maintenance of the healthy CNS. Interestingly, glial dysfunctions have proven to be the major contributor to neuronal loss in several CNS disorders and pathologies. Specifically, in the field of neuroAIDS, glial dysfunction–mediated neuronal stress is a major factor contributing to the HIV-1 neuropathogenesis. As there is increasing evidence that astrocytes harbor HIV-1 and serve as “safe haven” for the dormant virus in the brain, the indirect pathway of neuronal damage has taken over the direct neuronal damage in its contribution to HIV-1 neuropathogenesis. In this review, we provide a brief insight into the astrocyte functions and dysfunctions in different CNS conditions with an elaborated insight into neuroAIDS. Detailed understanding of the role of astrocytes in neuroAIDS will help in the better therapeutic management of the neurological problems associated with HIV-1 patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Al-Harti L, Joseph J, Nath A (2018) Astrocytes as an HIV CNS reservoir: highlights and reflections of an NIMH-sponsored symposium. J Neurovirol 24:665–669

    Article  PubMed  PubMed Central  Google Scholar 

  • Allen NJ, Bennett ML, Foo LC, Wang GX, Chakraborty C, Smith SJ, Barres BA (2012) Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature 486:410–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banerjee S, Walseth TF, Borgmann K, Wu L, Bidasee KR, Kannan MS, Ghorpade A (2008) CD38/cyclic ADP-ribose regulates astrocyte calcium signaling: implications for neuroinflammation and HIV-1-associated dementia. J NeuroImmune Pharmacol 3:154–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Barat C, Proust A, Deshiere A, Leboeuf M, Drouin J, Tremblay MJ (2018) Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency. Glia 66:1363–1381

    Article  PubMed  Google Scholar 

  • Bergles DE, Jahr CE (1998) Glial contribution to glutamate uptake at Schaffer collateral-commissural synapses in the hippocampus. J Neurosci 18:7709–7716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berman JW, Carvallo L, Buckner CM, Luers A, Prevedel L, Bennett MV, Eugenin EA (2016) HIV-tat alters Connexin43 expression and trafficking in human astrocytes: role in NeuroAIDS. J Neuroinflammation 13:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297–308

    Article  CAS  PubMed  Google Scholar 

  • Capo-Velez CM et al (2018) The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders. Sci Rep 8:1829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chauhan A, Mehla R, Vijayakumar TS, Handy I (2014) Endocytosis-mediated HIV-1 entry and its significance in the elusive behavior of the virus in astrocytes. Virology 456-457:1–19

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Christopherson KS, Ullian EM, Stokes CCA, Mullowney CE, Hell JW, Agah A, Lawler J, Mosher DF, Bornstein P, Barres BA (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120:421–433

    Article  CAS  PubMed  Google Scholar 

  • Churchill M, Nath A (2013) Where does HIV hide? A focus on the central nervous system. Curr Opin HIV AIDS 8:165–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Churchill MJ, Wesselingh SL, Cowley D, Pardo CA, McArthur JC, Brew BJ, Gorry PR (2009) Extensive astrocyte infection is prominent in human immunodeficiency virus-associated dementia. Ann Neurol 66:253–258

    Article  PubMed  Google Scholar 

  • Davey RT Jr et al (1999) HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A 96:15109–15114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dreyer EB, Lipton SA (1995) The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid. Eur J Neurosci 7:2502–2507

    Article  CAS  PubMed  Google Scholar 

  • Drogemuller K, Helmuth U, Brunn A, Sakowicz-Burkiewicz M, Gutmann DH, Mueller W, Deckert M, Schluter D (2008) Astrocyte gp130 expression is critical for the control of toxoplasma encephalitis. J Immunol 181:2683–2693

    Article  PubMed  Google Scholar 

  • Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23:1320–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elbirt D, Mahlab-Guri K, Bezalel-Rosenberg S, Gill H, Attali M, Asher I (2015) HIV-associated neurocognitive disorders (HAND). Isr Med Assoc J 17:54–59

    PubMed  Google Scholar 

  • Eroglu C, Allen NJ, Susman MW, O’Rourke NA, Park CY, Özkan E, Chakraborty C, Mulinyawe SB, Annis DS, Huberman AD, Green EM, Lawler J, Dolmetsch R, Garcia KC, Smith SJ, Luo ZD, Rosenthal A, Mosher DF, Barres BA (2009) Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell 139:380–392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eugenin EA, Clements JE, Zink MC, Berman JW (2011) Human immunodeficiency virus infection of human astrocytes disrupts blood-brain barrier integrity by a gap junction-dependent mechanism. J Neurosci 31:9456–9465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan Y, He JJ (2016a) HIV-1 tat induces unfolded protein response and endoplasmic reticulum stress in astrocytes and causes neurotoxicity through glial fibrillary acidic protein (GFAP) activation and aggregation. J Biol Chem 291:22819–22829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan Y, He JJ (2016b) HIV-1 tat promotes lysosomal exocytosis in astrocytes and contributes to astrocyte-mediated tat neurotoxicity. J Biol Chem 291:22830–22840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fatima M, Prajapati B, Saleem K, Kumari R, Mohindar Singh Singal C, Seth P (2017) Novel insights into role of miR-320a-VDAC1 axis in astrocyte-mediated neuronal damage in neuroAIDS. Glia 65:250–263

    Article  PubMed  Google Scholar 

  • Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143–2155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743

    Article  CAS  PubMed  Google Scholar 

  • Fitting S, McLaurin KA, Booze RM, Mactutus CF (2018) Dose-dependent neurocognitive deficits following postnatal day 10 HIV-1 viral protein exposure: relationship to hippocampal anatomy parameters. Int J Dev Neurosci 65:66–82

    Article  CAS  PubMed  Google Scholar 

  • Fu W, Shi D, Westaway D, Jhamandas JH (2015) Bioenergetic mechanisms in astrocytes may contribute to amyloid plaque deposition and toxicity. J Biol Chem 290:12504–12513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gangwani MR, Noel RJ Jr, Shah A, Rivera-Amill V, Kumar A (2013) Human immunodeficiency virus type 1 viral protein R (Vpr) induces CCL5 expression in astrocytes via PI3K and MAPK signaling pathways. J Neuroinflammation 10:136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez-Scarano F, Martin-Garcia J (2005) The neuropathogenesis of AIDS. Nat Rev Immunol 5:69–81

    Article  CAS  PubMed  Google Scholar 

  • Gorry PR, Howard JL, Churchill MJ, Anderson JL, Cunningham A, Adrian D, McPhee D, Purcell DF (1999) Diminished production of human immunodeficiency virus type 1 in astrocytes results from inefficient translation of gag, env, and nef mRNAs despite efficient expression of. Tat Rev J Virol 73:352–361

    CAS  PubMed  Google Scholar 

  • Gorry PR, Ong C, Thorpe J, Bannwarth S, Thompson K, Gatignol A, Wesselingh S, Purcell D (2003) Astrocyte infection by HIV-1: mechanisms of restricted virus replication, and role in the pathogenesis of HIV-1-associated dementia. Curr HIV Res 1:463–473

    Article  CAS  PubMed  Google Scholar 

  • Gray LR, Roche M, Flynn JK, Wesselingh SL, Gorry PR, Churchill MJ (2014) Is the central nervous system a reservoir of HIV-1? Curr Opin HIV AIDS 9:552–558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hao HN, Lyman WD (1999) HIV infection of fetal human astrocytes: the potential role of a receptor-mediated endocytic pathway. Brain Res 823:24–32

    Article  CAS  PubMed  Google Scholar 

  • Hasel P, Dando O, Jiwaji Z, Baxter P, Todd AC, Heron S, Márkus NM, McQueen J, Hampton DW, Torvell M, Tiwari SS, McKay S, Eraso-Pichot A, Zorzano A, Masgrau R, Galea E, Chandran S, Wyllie DJA, Simpson TI, Hardingham GE (2017) Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism. Nat Commun 8:15132

    Article  PubMed  PubMed Central  Google Scholar 

  • Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535:551–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, For the CHARTER Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER study. Neurology 75:2087–2096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henderson LJ, Sharma A, Monaco MC, Major EO, Al-Harthi L (2012) Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription through its intact core and cysteine-rich domains inhibits Wnt/beta-catenin signaling in astrocytes: relevance to HIV neuropathogenesis. J Neurosci 32:16306–16313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27:735–743

    Article  CAS  PubMed  Google Scholar 

  • Hill JD, Zuluaga-Ramirez V, Gajghate S, Winfield M, Persidsky Y (2019) Chronic intrahippocampal infusion of HIV-1 neurotoxic proteins: a novel mouse model of HIV-1 associated inflammation and neural stem cell dysfunction J Neuroimmune Pharmacol

  • Hoye ML, Regan MR, Jensen LA, Lake AM, Reddy LV, Vidensky S, Richard JP, Maragakis NJ, Rothstein JD, Dougherty JD, Miller TM (2018) Motor neuron-derived microRNAs cause astrocyte dysfunction in amyotrophic lateral sclerosis. Brain 141:2561–2575

    PubMed  PubMed Central  Google Scholar 

  • Hsiao HY, Chen YC, Chen HM, Tu PH, Chern Y (2013) A critical role of astrocyte-mediated nuclear factor-kappaB-dependent inflammation in Huntington’s disease. Hum Mol Genet 22:1826–1842

    Article  CAS  PubMed  Google Scholar 

  • Hua X, Malarkey EB, Sunjara V, Rosenwald SE, Li WH, Parpura V (2004) Ca(2+)-dependent glutamate release involves two classes of endoplasmic reticulum Ca(2+) stores in astrocytes. J Neurosci Res 76:86–97

    Article  CAS  PubMed  Google Scholar 

  • Jayadev S, Yun B, Nguyen H, Yokoo H, Morrison RS, Garden GA (2007) The glial response to CNS HIV infection includes p53 activation and increased expression of p53 target genes. J NeuroImmune Pharmacol 2:359–370

    Article  PubMed  Google Scholar 

  • Jiang R, Diaz-Castro B, Looger LL, Khakh BS (2016) Dysfunctional calcium and glutamate signaling in striatal astrocytes from Huntington’s disease model mice. J Neurosci 36:3453–3470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaul M, Garden GA, Lipton SA (2001) Pathways to neuronal injury and apoptosis in HIV-associated dementia. Nature 410:988–994

    Article  CAS  PubMed  Google Scholar 

  • Kim HA, Jiang L, Madsen H, Parish CL, Massalas J, Smardencas A, O’Leary C, Gantois I, O’Tuathaigh C, Waddington JL, Ehrlich ME, Lawrence AJ, Drago J (2014) Resolving pathobiological mechanisms relating to Huntington disease: gait, balance, and involuntary movements in mice with targeted ablation of striatal D1 dopamine receptor cells. Neurobiol Dis 62:323–337

    Article  CAS  PubMed  Google Scholar 

  • Koistinaho M, Lin S, Wu X, Esterman M, Koger D, Hanson J, Higgs R, Liu F, Malkani S, Bales KR, Paul SM (2004) Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nat Med 10:719–726

    Article  CAS  PubMed  Google Scholar 

  • Kou W, Banerjee S, Eudy J, Smith LM, Persidsky R, Borgmann K, Wu L, Sakhuja N, Deshpande MS, Walseth TF, Ghorpade A (2009) CD38 regulation in activated astrocytes: implications for neuroinflammation and HIV-1 brain infection. J Neurosci Res 87:2326–2339

    Article  CAS  PubMed  Google Scholar 

  • Kovacsics CE, Gill AJ, Ambegaokar SS, Gelman BB, Kolson DL (2017) Degradation of heme oxygenase-1 by the immunoproteasome in astrocytes: a potential interferon-gamma-dependent mechanism contributing to HIV neuropathogenesis. Glia 65:1264–1277

    Article  PubMed  PubMed Central  Google Scholar 

  • Kucukdereli H, Allen NJ, Lee AT, Feng A, Ozlu MI, Conatser LM, Chakraborty C, Workman G, Weaver M, Sage EH, Barres BA, Eroglu C (2011) Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC. Proc Natl Acad Sci U S A 108:E440–E449

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee S et al (2010) Channel-mediated tonic GABA release from glia science, vol 330, New York, NY, pp 790–796

  • Lehmann MH, Masanetz S, Kramer S, Erfle V (2006) HIV-1 Nef upregulates CCL2/MCP-1 expression in astrocytes in a myristoylation- and calmodulin-dependent manner. J Cell Sci 119:4520–4530

    Article  CAS  PubMed  Google Scholar 

  • Li GH, Anderson C, Jaeger L, Do T, Major EO, Nath A (2015) Cell-to-cell contact facilitates HIV transmission from lymphocytes to astrocytes via CXCR4. Aids 29:755–766

    Article  PubMed  Google Scholar 

  • Li GH, Henderson L, Nath A (2016) Astrocytes as an HIV reservoir: mechanism of HIV infection. Curr HIV Res 14:373–381

    Article  CAS  PubMed  Google Scholar 

  • Lian H, Zheng H (2016) Signaling pathways regulating neuron-glia interaction and their implications in Alzheimer’s disease. J Neurochem 136:475–491

    Article  CAS  PubMed  Google Scholar 

  • Lindsberg PJ, Roine RO (2004) Hyperglycemia in acute stroke. Stroke 35:363–364

    Article  PubMed  Google Scholar 

  • Liu X, Jana M, Dasgupta S, Koka S, He J, Wood C, Pahan K (2002) Human immunodeficiency virus type 1 (HIV-1) tat induces nitric-oxide synthase in human astroglia. J Biol Chem 277:39312–39319

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Shah A, Gangwani MR, Silverstein PS, Fu M, Kumar A (2014) HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors. Sci Rep 4:4450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 10:615–622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nana AL, Kim EH, Thu DC, Oorschot DE, Tippett LJ, Hogg VM, Synek BJ, Roxburgh R, Waldvogel HJ, Faull RL (2014) Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington’s disease. J Huntingtons Dis 3:45–64

    PubMed  Google Scholar 

  • Newman EA (2003) Glial cell inhibition of neurons by release of ATP. J Neurosci 23:1659–1666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nitkiewicz J, Borjabad A, Morgello S, Murray J, Chao W, Emdad L, Fisher PB, Potash MJ, Volsky DJ (2017) HIV induces expression of complement component C3 in astrocytes by NF-kappaB-dependent activation of interleukin-6 synthesis. J Neuroinflammation 14:23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nookala AR, Shah A, Noel RJ, Kumar A (2013) HIV-1 Tat-mediated induction of CCL5 in astrocytes involves NF-kappaB, AP-1, C/EBPalpha and C/EBPgamma transcription factors and JAK, PI3K/Akt and p38 MAPK signaling pathways. PLoS One 8:e78855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ong CL, Thorpe JC, Gorry PR, Bannwarth S, Jaworowski A, Howard JL, Chung S, Campbell S, Christensen HS, Clerzius G, Mouland AJ, Gatignol A, Purcell DFJ (2005) Low TRBP levels support an innate human immunodeficiency virus type 1 resistance in astrocytes by enhancing the PKR antiviral response. J Virol 79:12763–12772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orellana JA, Saez JC, Bennett MV, Berman JW, Morgello S, Eugenin EA (2014) HIV increases the release of dickkopf-1 protein from human astrocytes by a Cx43 hemichannel-dependent mechanism. J Neurochem 128:752–763

    Article  CAS  PubMed  Google Scholar 

  • Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747

    Article  CAS  PubMed  Google Scholar 

  • Persichini T, Mastrantonio R, Del Matto S, Palomba L, Cantoni O, Colasanti M (2014) The role of arachidonic acid in the regulation of nitric oxide synthase isoforms by HIV gp120 protein in astroglial cells. Free Radic Biol Med 74:14–20

    Article  CAS  PubMed  Google Scholar 

  • Putatunda R, Zhang Y, Li F, Yang XF, Barbe MF, Hu W (2018) Adult neurogenic deficits in HIV-1 Tg26 transgenic mice. J Neuroinflammation 15:287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ratai EM, Annamalai L, Burdo T, Joo CG, Bombardier JP, Fell R, Hakimelahi R, He J, Lentz MR, Campbell J, Curran E, Halpern EF, Masliah E, Westmoreland SV, Williams KC, González RG (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Richards MH, Narasipura SD, Kim S, Seaton MS, Lutgen V, Al-Harthi L (2015) Dynamic interaction between astrocytes and infiltrating PBMCs in context of neuroAIDS. Glia 63:441–451

    Article  PubMed  Google Scholar 

  • Roberts ES, Chana G, Nguyen TB, Perera G, Landau S, Rabe-Hesketh S, Glass JD, McArthur J, Everall IP (2013) The spatial relationship between neurons and astrocytes in HIV-associated dementia. J Neurovirol 19:123–130

    Article  PubMed  Google Scholar 

  • Robertson JM (2014) Astrocytes and the evolution of the human brain. Med Hypotheses 82:236–239

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Martin LJ, Kuncl RW (1992) Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326:1464–1468

    Article  CAS  PubMed  Google Scholar 

  • Sami Saribas A, Cicalese S, Ahooyi TM, Khalili K, Amini S, Sariyer IK (2017) HIV-1 Nef is released in extracellular vesicles derived from astrocytes: evidence for Nef-mediated neurotoxicity. Cell Death Dis 8:e2542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sardo L, Vakil PR, Elbezanti W, El-Sayed A, Klase Z (2016) The inhibition of microRNAs by HIV-1 tat suppresses beta catenin activity in astrocytes. Retrovirology 13:25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah A, Singh DP, Buch S, Kumar A (2011) HIV-1 envelope protein gp120 up regulates CCL5 production in astrocytes which can be circumvented by inhibitors of NF-kappaB pathway. Biochem Biophys Res Commun 414:112–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah A, Vaidya NK, Bhat HK, Kumar A (2016) HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1alpha, JNK and AP-1 pathway. Sci Rep 6:18929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheikhbahaei S, Turovsky EA, Hosford PS, Hadjihambi A, Theparambil SM, Liu B, Marina N, Teschemacher AG, Kasparov S, Smith JC, Gourine AV (2018) Astrocytes modulate brainstem respiratory rhythm-generating circuits and determine exercise capacity. Nat Commun 9:370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  CAS  PubMed  Google Scholar 

  • Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song S, Miranda CJ, Braun L, Meyer K, Frakes AE, Ferraiuolo L, Likhite S, Bevan AK, Foust KD, McConnell MJ, Walker CM, Kaspar BK (2016) Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis. Nat Med 22:397–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soo Youn G, Ju SM, Choi SY, Park J (2015) HDAC6 mediates HIV-1 tat-induced proinflammatory responses by regulating MAPK-NF-kappaB/AP-1 pathways in astrocytes glia

    Google Scholar 

  • Sultan S, Li L, Moss J, Petrelli F, Cassé F, Gebara E, Lopatar J, Pfrieger FW, Bezzi P, Bischofberger J, Toni N (2015) Synaptic integration of adult-born hippocampal neurons is locally controlled by astrocytes. Neuron 88:957–972

    Article  CAS  PubMed  Google Scholar 

  • Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swanson PA 2nd, McGavern DB (2015) Viral diseases of the central nervous system. Curr Opin Virol 11:44–54

    Article  PubMed  PubMed Central  Google Scholar 

  • Takahashi K, Wesselingh SL, Griffin DE, McArthur JC, Johnson RT, Glass JD (1996) Localization of HIV-1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry. Ann Neurol 39:705–711

    Article  CAS  PubMed  Google Scholar 

  • Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X, Nedergaard M (2006) Astrocyte-mediated control of cerebral blood flow. Nat Neurosci 9:260–267

    Article  CAS  PubMed  Google Scholar 

  • Teodorof-Diedrich C, Spector SA (2018) Human immunodeficiency virus type 1 gp120 and tat induce mitochondrial fragmentation and incomplete mitophagy in human neurons. J Virol 92

  • Tewari M, Monika VRK, Menon M, Seth P (2015) Astrocytes mediate HIV-1 Tat-induced neuronal damage via ligand-gated ion channel P2X7R. J Neurochem 132:464–476

    Article  CAS  PubMed  Google Scholar 

  • Thaney VE, Sanchez AB, Fields JA, Minassian A, Young JW, Maung R, Kaul M (2018) Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J Neurovirol 24:156–167

    Article  CAS  PubMed  Google Scholar 

  • Tornatore C, Chandra R, Berger JR, Major EO (1994) HIV-1 infection of subcortical astrocytes in the pediatric central nervous system. Neurology 44:481–487

    Article  CAS  PubMed  Google Scholar 

  • Walsh KA, Megyesi JF, Wilson JX, Crukley J, Laubach VE, Hammond RR (2004) Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity. J Neuroinflammation 1:8

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Pekarskaya O, Bencheikh M, Chao W, Gelbard HA, Ghorpade A, Rothstein JD, Volsky DJ (2003) Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120. Virology 312:60–73

    Article  CAS  PubMed  Google Scholar 

  • Williams R, Yao H, Dhillon NK, Buch SJ (2009) HIV-1 Tat co-operates with IFN-gamma and TNF-alpha to increase CXCL10 in human astrocytes. PLoS One 4:e5709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wyss-Coray T, Loike JD, Brionne TC, Lu E, Anankov R, Yan F, Silverstein SC, Husemann J (2003) Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med 9:453–457

    Article  CAS  PubMed  Google Scholar 

  • Wyss-Coray T, Masliah E, Toggas SM, Rockenstein EM, Brooker MJ, Lee HS, Mucke L (1996) Dysregulation of signal transduction pathways as a potential mechanism of nervous system alterations in HIV-1 gp120 transgenic mice and humans with HIV-1 encephalitis. J Clin Invest 97:789–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xing HQ, Zhang Y, Izumo K, Arishima S, Kubota R, Ye X, Xu Q, Mori K, Izumo S (2017) Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated neurocognitive disorders. Neuropathology 37:25–34

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Ge W, Chen Y, Zhang Z, Shen W, Wu C, Poo M, Duan S (2003) Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc Natl Acad Sci U S A 100:15194–15199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Youn GS, Cho H, Kim D, Choi SY, Park J (2017) Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes. Redox Biol 12:978–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou BY, Liu Y, Kim B, Xiao Y, He JJ (2004) Astrocyte activation and dysfunction and neuron death by HIV-1 Tat expression in astrocytes. Mol Cell Neurosci 27:296–305

    Article  CAS  PubMed  Google Scholar 

  • Zhuang K, Leda AR, Tsai L, Knight H, Harbison C, Gettie A, Blanchard J, Westmoreland S, Cheng-Mayer C (2014) Emergence of CD4 independence envelopes and astrocyte infection in R5 simian-human immunodeficiency virus model of encephalitis. J Virol 88:8407–8420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6:43–50

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge the support of the facilities provided under the Biotechnology Information System Network (BTISNET) grant, Department of Biotechnology, India and Distributed Information Centre at NBRC, Manesar, India.

Funding

The study was supported by a Research Fellowship to Hriday S. Pandey from CSIR, New Delhi, India, and financial support from Department of Biotechnology (DBT) and Department of Science and Technology (DST), New Delhi, and NBRC core funds to Prof. Pankaj Seth.

Author information

Authors and Affiliations

  1. Department of Cellular and Molecular Neuroscience, Neurovirology Section, National Brain Research Centre (NBRC), Nainwal Road, NH-8, Manesar, Gurgaon, Haryana, 122052, India

    Hriday Shanker Pandey & Pankaj Seth

Authors
  1. Hriday Shanker Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pankaj Seth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pankaj Seth.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pandey, H.S., Seth, P. Friends Turn Foe—Astrocytes Contribute to Neuronal Damage in NeuroAIDS. J Mol Neurosci 69, 286–297 (2019). https://doi.org/10.1007/s12031-019-01357-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-019-01357-1

Keywords

Search

Navigation