Skip to main content

Advertisement

SpringerLink
Log in

Modulation of BK Channel by MicroRNA-9 in Neurons After Exposure to HIV and Methamphetamine

  • ORIGINAL ARTICLE
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

MicroRNAs (miR) regulate phenotype and function of neurons by binding to miR-response elements (MRE) in the 3′ untranslated regions (3′UTR) of various messenger RNAs to inhibit translation. MiR expression can be induced or inhibited by environmental factors like drug exposure and viral infection, leading to changes in cellular physiology. We hypothesized that the effects of methamphetamine (MA) and human immunodeficiency virus (HIV)-infection in the brain will induce changes in miR expression, and have downstream regulatory consequences in neurons. We first used a PCR-based array to screen for differential expression of 380 miRs in frontal cortex autopsy tissues of HIV-positive MA abusers and matched controls. These results showed significantly increased expression of the neuron-specific miR-9. In vitro, we used SH-SY5Y cells, an experimental system for dopaminergic studies, to determine miR expression by quantitative PCR after exposure to MA in the presence or absence of conditioned media from HIV-infected macrophages. Again, we found that miR-9 was significantly increased compared to controls. We also examined the inwardly rectifying potassium channel, KCNMA1, which has alternative splice variants that contain an MRE to miR-9. We identified alternate 3′UTRs of KCNMA1 both in vitro and in the autopsy specimens and found differential splice variant expression of KCNMA1, operating via the increased miR-9. Our results suggest that HIV and MA -induced elevated miR-9, leading to suppression of MRE-containing splice variants of KCNMA1, which may affect neurotransmitter release in dopaminergic neurons.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Agrawal L, Louboutin JP, Marusich E, Reyes BA, Van Bockstaele EJ, Strayer DS (2010) Dopaminergic neurotoxicity of HIV-1 gp120: reactive oxygen species as signaling intermediates. Brain Res 1306:116–130

    Article  PubMed  CAS  Google Scholar 

  • Antinori A et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  PubMed  CAS  Google Scholar 

  • Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, Pearlson GD (1993) Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology 43:2099–2104

    Article  PubMed  CAS  Google Scholar 

  • Banerjee S, Neveu P, Kosik KS (2009) A coordinated local translational control point at the synapse involving relief from silencing and MOV10 degradation. Neuron 64:871–884

    Article  PubMed  CAS  Google Scholar 

  • Basso MR, Bornstein RA (2000) Neurobehavioural consequences of substance abuse and HIV infection. J Psychopharmacol 14:228–237

    Article  PubMed  CAS  Google Scholar 

  • Beck AT (1992) Beck depression inventory manual. Psychological Corporation, San Antonio

    Google Scholar 

  • Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    Article  PubMed  CAS  Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc B 57:289–300

    Google Scholar 

  • Brabers NA, Nottet HS (2006) Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur J Clin Invest 36:447–458

    Article  PubMed  CAS  Google Scholar 

  • Brady AM, Glick SD, O’Donnell P (2003) Changes in electrophysiological properties of nucleus accumbens neurons depend on the extent of behavioral sensitization to chronic methamphetamine. Ann N Y Acad Sci 1003:358–363

    Article  PubMed  CAS  Google Scholar 

  • Branch SY, Beckstead MJ (2012) Methamphetamine produces bidirectional, concentration-dependent effects on dopamine neuron excitability and dopamine-mediated synaptic currents. J Neurophysiol 108:802–809

    Article  PubMed  PubMed Central  Google Scholar 

  • Butler A, Tsunoda S, McCobb DP, Wei A, Salkoff L (1993) mSlo, a complex mouse gene encoding “maxi” calcium-activated potassium channels. Science 261:221–224

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekar V, Dreyer JL (2009) microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity. Mol Cell Neurosci 42:350–362

    Article  PubMed  CAS  Google Scholar 

  • Chang L, Wang G-J, Volkow ND, Ernst T, Telang F, Logan J, Fowler JS (2008) Decreased brain dopamine transporters are related to cognitive deficits in HIV patients with or without cocaine abuse. Neuroimage 42:869–878

    Article  PubMed  PubMed Central  Google Scholar 

  • Cherner M, Masliah E, Ellis RJ, Marcotte TD, Moore DJ, Grant I, Heaton RK (2002) Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis. Neurology 59:1563–1567

    Article  PubMed  CAS  Google Scholar 

  • Clark AM, Goldstein LD, Tevlin M, Tavare S, Shaham S, Miska EA (2010) The microRNA miR-124 controls gene expression in the sensory nervous system of Caenorhabditis elegans. Nucleic Acids Res 38:3780–3793

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Colfax G, Shoptaw S (2005) The methamphetamine epidemic: implications for HIV prevention and treatment. Curr HIV/AIDS Rep 2:194–199

    Article  PubMed  Google Scholar 

  • Couper FJ, Logan BK (2004) Drugs and human performance fact sheets. National Highway Traffic Safety Administration, Department of Transportation, Washington, DC, pp 62–63

    Google Scholar 

  • Cubells JF, Rayport S, Rajendran G, Sulzer D (1994) Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress. J Neurosci 14:2260–2271

    PubMed  CAS  Google Scholar 

  • Cuellar TL, Davis TH, Nelson PT, Loeb GB, Harfe BD, Ullian E, McManus MT (2008) Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc Natl Acad Sci U S A 105:5614–5619

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Cysique LA, Brew BJ (2009) Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev 19:169–185

    Article  PubMed  Google Scholar 

  • da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57

    Article  CAS  Google Scholar 

  • Davies JQ, Gordon S (2004) Isolation and culture of human macrophages. In: Helgason CD, Miller CL (eds) Basic cell culture protocols, 3rd edn. Humana Press, Totowa, pp 105–116

    Chapter  Google Scholar 

  • Derlet RW, Horowitz BZ (1995) Cardiotoxic drugs. Emerg Med Clin North Am 13:771–791

    PubMed  CAS  Google Scholar 

  • Dreyer JL (2010) New insights into the roles of microRNAs in drug addiction and neuroplasticity. Genome Med 2:92

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Durell TM, Kroutil LA, Crits-Christoph P, Barchha N, Van Brunt DL (2008) Prevalence of nonmedical methamphetamine use in the United States. Subst Abuse Treat Prev Policy 3:19

    Article  PubMed  PubMed Central  Google Scholar 

  • Eletto D, Russo G, Passiatore G, Del Valle L, Giordano A, Khalili K, Gualco E, Peruzzi F (2008) Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a. J Cell Physiol 216:764–770

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, Gelman BB, Vaida F, Collier A, Marra CM, Ances B, Atkinson JH, Dworkin RH, Morgello S, Grant I (2010) Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 67:552–558

    Article  PubMed  Google Scholar 

  • Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V, Gallego C, Comella JX (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75:991–1003

    Article  PubMed  CAS  Google Scholar 

  • Faber ES, Sah P (2003) Calcium-activated potassium channels: multiple contributions to neuronal function. Neuroscientist 9:181–194

    Article  PubMed  CAS  Google Scholar 

  • Fang CT, Chang YY, Hsu HM, Twu SJ, Chen KT, Lin CC, Huang LY, Chen MY, Hwang JS, Wang JD, Chuang CY (2007) Life expectancy of patients with newly-diagnosed HIV infection in the era of highly active antiretroviral therapy. QJM 100:97–105

    Article  PubMed  CAS  Google Scholar 

  • First MB (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC

    Google Scholar 

  • Fischer JF, Cho AK (1979) Chemical release of dopamine from striatal homogenates: evidence for an exchange diffusion model. J Pharmacol Exp Ther 208:203–209

    PubMed  CAS  Google Scholar 

  • Frohman MA, Dush MK, Martin GR (1988) Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A 85:8998–9002

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Fukuda Y, Kawasaki H, Taira K (2005) Exploration of human miRNA target genes in neuronal differentiation. Nucleic Acids Symp Ser (Oxf) 49:341–342

    Google Scholar 

  • Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233:215–219

    Article  PubMed  CAS  Google Scholar 

  • Gendelman HE, Ding S, Gong N, Liu J, Ramirez SH, Persidsky Y, Mosley RL, Wang T, Volsky DJ, Xiong H (2009) Monocyte chemotactic protein-1 regulates voltage-gated K + channels and macrophage transmigration. J Neuroimmune Pharmacol 4:47–59

    Article  PubMed  PubMed Central  Google Scholar 

  • Gonzales R, Mooney L, Rawson RA (2010) The methamphetamine problem in the United States. Annu Rev Public Health 31:385–398

    Article  PubMed  Google Scholar 

  • Hasin DS, Trautman KD, Miele GM, Samet S, Smith M, Endicott J (1996) Psychiatric research interview for substance and mental disorders (PRISM): reliability for substance abusers. Am J Psychiatry 153:1195–1201

    PubMed  CAS  Google Scholar 

  • Heaton RK et al (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy: CHARTER Study. Neurology 75:2087–2096

    Article  PubMed  PubMed Central  Google Scholar 

  • Houzet L, Yeung M, de Lame V, Desai D, Smith S, Jeang K-T (2008) MicroRNA profile changes in human immunodeficiency virus type 1 (HIV-1) seropositive individuals. Retrovirology 5:118

    Article  PubMed  PubMed Central  Google Scholar 

  • Keselman HJ, Rogan JC (1977) The Tukey multiple comparison test: 1953–1976. Psychological Bulletin 84:1050–1056

    Article  Google Scholar 

  • Kogan FJ, Nichols WK, Gibb JW (1976) Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels. Eur J Pharmacol 36:363–371

    Article  PubMed  CAS  Google Scholar 

  • Kosik KS (2006) The neuronal microRNA system. Nat Rev Neurosci 7:911–920

    Article  PubMed  CAS  Google Scholar 

  • Kraft-Terry SD, Buch SJ, Fox HS, Gendelman HE (2009) A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection. Neuron 64:133–145

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kramer CY (1956) Extension of multiple range tests to group means with unequal number of replications. Biometrics 12:307–310

    Article  Google Scholar 

  • Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lancaster B, Nicoll RA (1987) Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J Physiol 389:187–203

    PubMed  CAS  PubMed Central  Google Scholar 

  • Letendre SL, Cherner M, Ellis RJ, Marquie-Beck J, Gragg B, Marcotte T, Heaton RK, McCutchan JA, Grant I (2005) The effects of hepatitis C, HIV, and methamphetamine dependence on neuropsychological performance: biological correlates of disease. AIDS 19(Suppl 3):S72–78

    Article  PubMed  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Maxwell JC, Rutkowski BA (2008) The prevalence of methamphetamine and amphetamine abuse in North America: a review of the indicators, 1992–2007. Drug Alcohol Rev 27:229–235

    Article  PubMed  Google Scholar 

  • Melrose RJ, Tinaz S, Castelo JM, Courtney MG, Stern CE (2008) Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing. Behav Brain Res 188:337–347

    Article  PubMed  Google Scholar 

  • Mikl M, Vendra G, Doyle M, Kiebler MA (2010) RNA localization in neurite morphogenesis and synaptic regulation: current evidence and novel approaches. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 196:321–334

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Nuovo GJ (2010) In situ detection of microRNAs in paraffin embedded, formalin fixed tissues and the co-localization of their putative targets. Methods 52:307–315

    Article  PubMed  CAS  Google Scholar 

  • Obernosterer G, Martinez J, Alenius M (2007) Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. Nat Protoc 2:1508–1514

    Article  PubMed  CAS  Google Scholar 

  • Pacifici M, Delbue S, Ferrante P, Jeansonne D, Kadri F, Nelson S, Velasco-Gonzalez C, Zabaleta J, Peruzzi F (2012) Cerebrospinal fluid miRNA profile in HIV-encephalitis. J Cell Physiol 228(5):1070–1075

    Google Scholar 

  • Pietrzykowski AZ (2010) The role of microRNAs in drug addiction: a big lesson from tiny molecules. Int Rev Neurobiol 91:1–24

    Article  PubMed  CAS  Google Scholar 

  • Pietrzykowski AZ, Friesen RM, Martin GE, Puig SI, Nowak CL, Wynne PM, Siegelmann HT, Treistman SN (2008) Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. Neuron 59:274–287

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Popovic M, Gartner S (1989) Biology of human imunodeficiency virus: virus receptor and cell tropism. Curr Opin Immunol 1:516–520

    Article  PubMed  CAS  Google Scholar 

  • Pruitt KD, Tatusova T, Klimke W, Maglott DR (2009) NCBI reference sequences: current status, policy and new initiatives. Nucleic Acids Res 37:D32–36

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Pulliam L, Herndier BG, Tang NM, McGrath MS (1991) Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. J Clin Invest 87:503–512

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991) Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathol 82:39–44

    Article  PubMed  CAS  Google Scholar 

  • Saas P, Walker PR, Quiquerez AL, Chalmers DE, Arrighi JF, Lienard A, Boucraut J, Dietrich PY (2002) A self-defence mechanism of astrocytes against Fas-mediated death involving interleukin-8 and CXCR2. Neuroreport 13:1921–1924

    Article  PubMed  CAS  Google Scholar 

  • Salkoff L, Butler A, Ferreira G, Santi C, Wei A (2006) High-conductance potassium channels of the SLO family. Nat Rev Neurosci 7:921–931

    Article  PubMed  CAS  Google Scholar 

  • Sandoval V, Riddle EL, Ugarte YV, Hanson GR, Fleckenstein AE (2001) Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model. J Neurosci 21:1413–1419

    PubMed  CAS  Google Scholar 

  • Sardar AM, Czudek C, Reynolds GP (1996) Dopamine deficits in the brain: the neurochemical basis of parkinsonian symptoms in AIDS. Neuroreport 7:910–912

    Article  PubMed  CAS  Google Scholar 

  • Sartor GC, St Laurent G 3rd, Wahlestedt C (2012) The emerging role of non-coding RNAs in drug addiction. Front Genet 3:106

    PubMed  CAS  PubMed Central  Google Scholar 

  • Sathyan P, Golden HB, Miranda RC (2007) Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. J Neurosci 27:8546–8557

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Storm JF (1987) Intracellular injection of a Ca2+ chelator inhibits spike repolarization in hippocampal neurons. Brain Res 435:387–392

    Article  PubMed  CAS  Google Scholar 

  • Tatro ET, Scott ER, Nguyen TL, Salaria S, Baneerje S, Masliah E, Everall IP, Achim CL (2010) Evidence for Alteration of Gene Regulatory Networks through MicroRNA's of the HIV-Infected Brain: Novel Analysis of Retrospective Cases. PLoS ONE (4):e10337. doi:10.1371/journal.pone.0010337.

  • Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, Fowler JS (2004) Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain 127:2452–2458

    Article  PubMed  Google Scholar 

  • Wang LL, Zhang Z, Li Q, Yang R, Pei X, Xu Y, Wang J, Zhou SF, Li Y (2009) Ethanol exposure induces differential microRNA and target gene expression and teratogenic effects which can be suppressed by folic acid supplementation. Hum Reprod 24:562–579

    Article  PubMed  CAS  Google Scholar 

  • Witwer KW, Sarbanes SL, Liu J, Clements JE (2011) A plasma microRNA signature of acute lentiviral infection: biomarkers of central nervous system disease. AIDS 25:2057–2067

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Woods SP, Rippeth JD, Frol AB, Levy JK, Ryan E, Soukup VM, Hinkin CH, Lazzaretto D, Cherner M, Marcotte TD, Gelman BB, Morgello S, Singer EJ, Grant I, Heaton RK (2004) Interrater reliability of clinical ratings and neurocognitive diagnoses in HIV. J Clin Exp Neuropsychol 26:759–778

    Article  PubMed  Google Scholar 

  • Wright SP, O’Brien RG (1988) Power analysis in an enhanced GLM procedure: what it might look like. In: SUGI 1988. Cary, NC, pp 1097–1102

    Google Scholar 

  • Wu L, Zhao Q, Zhu X, Peng M, Jia C, Wu W, Zheng J, Wu XZ (2010) A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain. Brain Pathol 20:1042–1054

    Article  PubMed  CAS  Google Scholar 

  • Yuva-Aydemir Y, Simkin A, Gascon E, Gao FB (2011) MicroRNA-9: functional evolution of a conserved small regulatory RNA. RNA Biol 8:557–564

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants DA031591 (E. Tatro) and P30MH062512 (C. Achim). Tissue samples and facilities and equipment were supported by the following NIH-funded programs: Translational Methamphetamine AIDS Research Center (DA026306), HIV Neurobehavioral Research Center (MH062512), California NeuroAIDS Tissue Network (MH083506), the Genomics and Molecular Biology Cores at the UCSD Center for AIDS Research (AI36214), the VA San Diego Health Care System, and the San Diego Veterans Medical Research Foundation. We thank Anya Umlaf for statistical consultation.

Conflicts of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA

    Erick T. Tatro, Shannon Hefler, Stephanie Shumaker-Armstrong, Benchawanna Soontornniyomkij, Michael Yang, Alex Yermanos, Nina Wren, David J. Moore & Cristian L. Achim

Authors
  1. Erick T. Tatro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shannon Hefler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephanie Shumaker-Armstrong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benchawanna Soontornniyomkij
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alex Yermanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nina Wren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David J. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cristian L. Achim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erick T. Tatro.

Electronic supplementary material

ESM 1

(PDF 178 kb)

ESM 2

(XLS 266 kb)

ESM 3

(XLS 140 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tatro, E.T., Hefler, S., Shumaker-Armstrong, S. et al. Modulation of BK Channel by MicroRNA-9 in Neurons After Exposure to HIV and Methamphetamine. J Neuroimmune Pharmacol 8, 1210–1223 (2013). https://doi.org/10.1007/s11481-013-9446-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-013-9446-8

Keywords

Search

Navigation