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Quantitation of parvalbumin+ neurons and human immunodeficiency virus type 1 (HIV-1) regulatory gene expression in the HIV-1 transgenic rat: effects of vitamin A deficiency and morphine

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Abstract

Vitamin A (VA) deficiency in human immunodeficiency virus (HIV) infection has been associated with more progressive HIV disease, which may be enhanced by opioid use. In these studies, we examined the effects of VA deficiency and morphine on frontal cortex neuronal numbers in the HIV-1 transgenic (Tg) rat. These studies showed that total numbers of neurons were similar for rats on the VA-deficient diet as for rats on the normal diet and these numbers were not affected by treatment with morphine. In contrast, numbers of neurons that expressed the calcium-binding protein parvalbumin, which is a marker interneurons that express the inhibitory neurotransmitter γ-aminobutyric acid (GABAergic neurons) were decreased for wild-type (Wt) rats on the VA-deficient diet and for Wt rats treated with morphine. In addition, parvalbumin+ neurons were also decreased for Tg rats on a normal diet but increased to normal levels when these animals were placed on the VA-deficient diet and treated with morphine. Analysis of expression of the genes that code for the HIV regulatory proteins vif, vpr, nef, and tat in frontal cortex and adjacent subcortical white matter showed that tat expression was increased in the morphine-treated Tg rat on the VA-deficient diet as compared to untreated Tg rats on the normal diet and untreated VA-deficient rats. These studies therefore suggest that VA deficiency, opioid exposure, and HIV infection alone and in combination may potentially alter neuronal metabolic activity and induce cellular stress, resulting in the observed changes in levels of parvalbumin expression. The specific mechanisms that underlie these effects require further study.

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References

  • Anthony IC, Bell JE (2008). The neuropathology of HIV/AIDS. Int Rev Psychiatry 20: 15–24.

    Article  PubMed  CAS  Google Scholar 

  • Bell JE (2004). An update on the neuropathology of HIV in the HAART era. Histopathology 45: 549–559.

    Article  PubMed  CAS  Google Scholar 

  • Bell JE, Brettle RP, Chiswick A, Simmonds P (1998). HIV encephalitis, proviral load and dementia in drug users and homosexuals with AIDS. Effect of neocortical involvement. Brain 121: 2043–2052.

    Article  PubMed  Google Scholar 

  • Benalal D, Bachrach U (1985). Opiates and cultured neuroblastoma × glioma cells. Effect on cyclic AMP and polyamine levels and on ornithine decarboxylase and protein kinase activities. Biochem J 227: 389–395.

    PubMed  CAS  Google Scholar 

  • Benes FM, Berretta S (2001). GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25: 1–27.

    Article  PubMed  CAS  Google Scholar 

  • Bruce-Keller AJ, Turchan-Cholewo J, Smart EJ, Geurin T, Chauhan A, Reid R, Xu R, Nath A, Knapp PE, Hauser KF (2008). Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV-1 Tat transgenic mice. Glia 56: 1414–1427.

    Article  PubMed  Google Scholar 

  • Carman JA, Hayes CE (1991). Abnormal regulation of IFN-gamma secretion in vitamin A deficiency. J Immunol 147: 1247–1252.

    PubMed  CAS  Google Scholar 

  • Cedeno-Laurent F, Bryant J, Fishelevich R, Jones OD, Deng A, Eng ML, Gaspari AA, Trujillo JR (2009). Inflammatory papillomatous hyperplasia and epidermal necrosis in a transgenic rat for HIV-1. J Dermatol Sci 53: 112–119.

    Article  PubMed  CAS  Google Scholar 

  • Cochran SM, Fujimura M, Morris BJ, Pratt JA (2002). Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain. Synapse 46: 206–214.

    Article  PubMed  CAS  Google Scholar 

  • Cysique LA, Maruff P, Brew BJ (2004). Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J NeuroVirol 10: 350–357.

    Article  PubMed  Google Scholar 

  • Dekkers J, Greensmith L, Navarrete R (2002). Changes in the expression of parvalbumin immunoreactivity in the lumbar spinal cord of the rat following neonatal nerve injury. Dev Neurosci 24: 283–293.

    Article  PubMed  CAS  Google Scholar 

  • Freund TF (2003). Interneuron Diversity series: rhythm and mood in perisomatic inhibition. Trends Neurosci 26: 489–495.

    Article  PubMed  CAS  Google Scholar 

  • Gerfen CR, Baimbridge KG, Miller JJ (1985). The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acad Sci U S A 82: 8780–8784.

    Article  PubMed  CAS  Google Scholar 

  • Gerstein M, Huleihel M, Mane R, Stilman M, Kashtuzki I, Hallak M, Golan H (2005). Remodeling of hippocampal GABAergic system in adult offspring after maternal hypoxia and magnesium sulfate load: immunohistochemical study. Exp Neurol 196: 18–29.

    Article  PubMed  CAS  Google Scholar 

  • Gibson JR, Beierlein M, Connors BW (1999). Two networks of electrically coupled inhibitory neurons in neocortex. Nature 402: 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Giunta B, Hou H, Zhu Y, Rrapo E, Tian J, Takashi M, Commins D, Singer E, He J, Fernandez F, Tan J (2009). HIV-1 Tat contributes to Alzheimer’s disease-like pathology in PSAPP mice. Int J Clin Exp Pathol 2: 433–443.

    PubMed  CAS  Google Scholar 

  • Gonzalez-Burgos G, Lewis DA (2008). GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull 34: 944–961.

    Article  PubMed  Google Scholar 

  • Gurwell JA, Nath A, Sun Q, Zhang J, Martin KM, Chen Y, Hauser KF (2001). Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro. Neuroscience 102: 555–563.

    Article  PubMed  CAS  Google Scholar 

  • Hauser KF, Hahn YK, Adjan VV, Zou S, Buch SK, Nath A, Bruce-Keller AJ, Knapp PE (2009). HIV-1 Tat and morphine have interactive effects on oligodendrocyte survival and morphology. Glia 57: 194–206.

    Article  PubMed  Google Scholar 

  • Hohmann P, Greene RS (1990). Retinoid induced changes in cAMP-dependent protein kinase activity detected by a new minigel assay. FEBS Lett 261: 81–84.

    Article  PubMed  CAS  Google Scholar 

  • Hu Y, Lund IV, Gravielle MC, Farb DH, Brooks-Kayal AR, Russek SJ (2008). Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor. J Biol Chem 283: 9328–9340.

    Article  PubMed  CAS  Google Scholar 

  • Keilhoff G, Becker A, Grecksch G, Wolf G, Bernstein HG (2004). Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia. Neuroscience 126: 591–598.

    Article  PubMed  CAS  Google Scholar 

  • Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM (2006). A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci 26: 1604–615.

    Article  PubMed  CAS  Google Scholar 

  • Langford D, Adame A, Grigorian A, Grant I, McCutchan JA, Ellis RJ, Marcotte TD, Masliah E (2003). Patterns of selective neuronal damage in methamphetamine-user AIDS patients. J Acquir Immune Defic Syndr 34: 467–474.

    Article  PubMed  CAS  Google Scholar 

  • Lewis DA, Moghaddam B (2006). Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations. Arch Neurol 63: 1372–1376.

    Article  PubMed  Google Scholar 

  • Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995). Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol 37: 373–380.

    Article  PubMed  CAS  Google Scholar 

  • Maharajan P, Prencipe R, Di Francesco P, Paino G, Ravagnan G, Maharajan V (2000). Maternal morphine alters parvalbumin immunoreactivity patterns in neonatal mouse brain. Synapse 35: 265–271.

    Article  PubMed  CAS  Google Scholar 

  • Mamiya T, Noda Y, Ren X, Hamdy M, Furukawa S, Kameyama T, Yamada K, Nabeshima T (2001). Involvement of cyclic AMP systems in morphine physical dependence in mice: prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor. Br J Pharmacol 132: 1111–1117.

    Article  PubMed  CAS  Google Scholar 

  • Maret S, Franken P, Dauvilliers Y, Ghyselinck NB, Chambon P, Tafti M (2005). Retinoic acid signaling affects cortical synchrony during sleep. Science 310: 111–113.

    Article  PubMed  CAS  Google Scholar 

  • Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA (1992). Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 51: 585–593.

    Article  PubMed  CAS  Google Scholar 

  • Perez-Casanova A, Noel RJ, Jr., Rivera-Amill V, Husain K, Kumar A (2007). Morphine-mediated deterioration of oxidative stress leads to rapid disease progression in SIV/SHIV-infected macaques. AIDS Res Hum Retroviruses 23: 1004–1007.

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Gekker G, Hu S, Anderson WR, Kravitz F, Portoghese PS, Balfour HH Jr, Chao CC (1994). Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells. J Neuroimmunol 50: 167–175.

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Gekker G, Hu S, Lokensgard J, Portoghese PS, Chao CC (1999). Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor. Neuropharmacology 38: 273–278.

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Gekker G, Schut R, Hu S, Balfour HH, Jr., Chao CC (1993). Enhancement of HIV-1 replication by opiates and cocaine: the cytokine connection. Adv Exp Med Biol 335: 181–188.

    Article  PubMed  CAS  Google Scholar 

  • Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH, Jr. (1990). Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 4: 869–873.

    Article  PubMed  CAS  Google Scholar 

  • Potter JD, Dedman JR, Means AR (1977). Ca2+-dependent regulation of cyclic-AMP phosphodiesterase by parvalbumin. J Biol Chem 252: 5609–5611.

    PubMed  CAS  Google Scholar 

  • Reid W, Abdelwahab S, Sadowska M, Huso D, Neal A, Ahearn A, Bryant J, Gallo RC, Lewis GK, Reitz M (2004). HIV-1 transgenic rats develop T cell abnormalities. Virology 321: 111–119.

    Article  PubMed  CAS  Google Scholar 

  • Reid W, Sadowska M, Denaro F, Rao S, Foulke J Jr, Hayes N, Jones O, Doodnauth D, Davis H, Sill A, O’Driscoll P, Huso D, Fouts T, Lewis G, Hill M, Kamin-Lewis R, Wei C, Ray P, Gallo RC, Reitz M, Bryant J (2001). An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci U S A 98: 9271–9276.

    Article  PubMed  CAS  Google Scholar 

  • Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002). HIV-associated cognitive impairment before and after the advent of combination therapy. J NeuroVirol 8: 136–142.

    Article  PubMed  Google Scholar 

  • Schwaller B, Tetko IV, Tandon P, Silveira DC, Vreugdenhil M, Henzi T, Potier MC, Celio MR, Villa AE (2004). Parvalbumin deficiency affects network properties resulting in increased susceptibility to epileptic seizures. Mol Cell Neurosci 25: 650–663.

    Article  PubMed  CAS  Google Scholar 

  • Semba RD, Graham NM, Caiaffa WT, Margolick JB, Clement L, Vlahov D (1993). Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med 153: 2149–2154.

    Article  PubMed  CAS  Google Scholar 

  • Sharma SK, Nirenberg M, Klee WA (1975). Morphine receptors as regulators of adenylate cyclase activity. Proc Natl Acad Sci U S A 72: 590–594.

    Article  PubMed  CAS  Google Scholar 

  • Traber J, Gullis R, Hamprecht B (1975). Influence of opiates on the levels of adenosine 3′:5′-cyclic monophosphate in neuroblastoma X glioma hybrid cells. Life Sci 16: 1863–1868.

    Article  PubMed  CAS  Google Scholar 

  • Trono D (1995). HIV accessory proteins: leading roles for the supporting cast. Cell 82: 189–192.

    Article  PubMed  CAS  Google Scholar 

  • Vigorito M, Lashomb AL, Chang SL (2007). Spatial learning and memory in HIV-1 transgenic rats. J Neuroimmune Pharmacol 2: 319–328.

    Article  PubMed  Google Scholar 

  • Wiley CA, Masliah E, Morey M, Lemere C, DeTeresa R, Grafe M, Hansen L, Terry R (1991). Neocortical damage during HIV infection. Ann Neurol 29: 651–657.

    Article  PubMed  CAS  Google Scholar 

  • Winer J, Jung CK, Shackel I, Williams PM (1999). Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270: 41–49.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Walter Royal.

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Sultana, S., Li, H., Puche, A. et al. Quantitation of parvalbumin+ neurons and human immunodeficiency virus type 1 (HIV-1) regulatory gene expression in the HIV-1 transgenic rat: effects of vitamin A deficiency and morphine. Journal of NeuroVirology 16, 33–40 (2010). https://doi.org/10.3109/13550280903555712

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  • DOI: https://doi.org/10.3109/13550280903555712

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