Skip to main content

Advertisement

SpringerLink
Log in

In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain

  • Original Article
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

Most individuals living with HIV in the USA are over 45 years old and are vulnerable to the combined effects of HIV and aging. Antiretroviral therapies reduce HIV morbidity and mortality but do not prevent HIV trans-activator of transcription (Tat) protein expression or development of HIV-associated neurocognitive disorder (HAND), which may be caused by Tat. Tat-transgenic (Tat-tg) mice are used to study Tat’s effects, typically after transgene induction with doxycycline. However, uninduced Tat-tg mice experience transgene leak and model aspects of HAND when aged, including neuroinflammation. We used in vivo 9.4-tesla proton magnetic resonance spectroscopy to compare neurochemistry in aged versus young female and male uninduced Tat-tg mice. Aged Tat-tg mice demonstrated measurable tat mRNA brain expression and had lower medial prefrontal cortex (MPFC) GABA, glutamate, and taurine levels and lower striatal GABA and taurine levels. Females had lower MPFC glutathione and taurine and lower striatal taurine levels. Brain testosterone levels were negatively correlated with age in aged males but not females. Aged mice had cortical abnormalities not previously reported in aged wild-type mice including lower MPFC GABA and taurine levels. As glutathione and taurine levels reflect inflammation and oxidative stress, our data suggest that Tat may exacerbate these processes in aged Tat-tg mice. However, additional studies in controls not expressing Tat are needed to confirm this point and to deconvolve individual effects of age and Tat expression. Sex steroid hormone supplements, which counter climacteric effects, increase taurine levels, and reduce inflammation and oxidative stress, could attenuate some of the brain abnormalities we identified in aged Tat-tg mice.

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

Similar content being viewed by others

References

  1. Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2014–2018. HIV Surveillance Supplemental Report. 2020:2020.

  2. Mackiewicz MM, Overk C, Achim CL, Masliah E. Pathogenesis of age-related HIV neurodegeneration. J Neurovirol. 2019;25:622–33.

    Article  CAS  PubMed  Google Scholar 

  3. Saylor D, Dickens AM, Sacktor N, Haughey N, Slusher B, Pletnikov M, et al. HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol. 2016;12:234–48.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mediouni S, Chinthalapudi K, Ekka MK, Usui I, Jablonski JA, Clementz MA, et al. Didehydro-Cortistatin A Inhibits HIV-1 by Specifically Binding to the Unstructured Basic Region of Tat. MBio. 2019;10. https://doi.org/10.1128/mBio.02662-18.

  5. Mediouni S, Darque A, Baillat G, Ravaux I, Dhiver C, Tissot-Dupont H, et al. Antiretroviral therapy does not block the secretion of the human immunodeficiency virus tat protein. Infect Disord Drug Targets. 2012;12:81–6.

    Article  CAS  PubMed  Google Scholar 

  6. Johnson TP, Patel K, Johnson KR, Maric D, Calabresi PA, Hasbun R, et al. Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein. Proc Natl Acad Sci U S A. 2013;110:13588–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Henderson LJ, Johnson TP, Smith BR, Reoma LB, Santamaria UA, Bachani M, et al. Presence of Tat and transactivation response element in spinal fluid despite antiretroviral therapy. AIDS. 2019;33(Suppl 2):S145–57.

    Article  CAS  PubMed  Google Scholar 

  8. Lawson MA, Kelley KW, Dantzer R. Intracerebroventricular administration of HIV-1 Tat induces brain cytokine and indoleamine 2,3-dioxygenase expression: a possible mechanism for AIDS comorbid depression. Brain Behav Immun. 2011;25:1569–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Carey AN, Sypek EI, Singh HD, Kaufman MJ, McLaughlin JP. Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse. Behav Brain Res. 2012;229:48–56.

    Article  CAS  PubMed  Google Scholar 

  10. Fitting S, Ignatowska-Jankowska BM, Bull C, Skoff RP, Lichtman AH, Wise LE, et al. Synaptic dysfunction in the hippocampus accompanies learning and memory deficits in human immunodeficiency virus type-1 Tat transgenic mice. Biol Psychiatry. 2013;73:443–53.

    Article  CAS  PubMed  Google Scholar 

  11. Paris JJ, Singh HD, Ganno ML, Jackson P, McLaughlin JP. Anxiety-like behavior of mice produced by conditional central expression of the HIV-1 regulatory protein, Tat. Psychopharmacology. 2014;231:2349–60.

    Article  CAS  PubMed  Google Scholar 

  12. Kesby JP, Markou A, Semenova S. The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice. Neuropharmacology. 2016;109:205–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Marks WD, Paris JJ, Schier CJ, Denton MD, Fitting S, McQuiston AR, et al. HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations. J Neurovirol. 2016;22:747–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. McLaughlin JP, Paris JJ, Mintzopoulos D, Hymel KA, Kim JK, Cirino TJ, et al. Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein Expression Induces Depression-like Effects and Oxidative Stress. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017;2:599–609.

    PubMed  PubMed Central  Google Scholar 

  15. Qrareya AN, Mahdi F, Kaufman MJ, Ashpole NM, Paris JJ. HIV-1 Tat promotes age-related cognitive, anxiety-like, and antinociceptive impairments in female mice that are moderated by aging and endocrine status. Geroscience. 2020. https://doi.org/10.1007/s11357-020-00268-z.

  16. Salahuddin MF, Qrareya AN, Mahdi F, Jackson D, Foster M, Vujanovic T, et al. Combined HIV-1 Tat and oxycodone activate the hypothalamic-pituitary-adrenal and -gonadal axes and promote psychomotor, affective, and cognitive dysfunction in female mice. Horm Behav. 2020;119:104649.

    Article  CAS  PubMed  Google Scholar 

  17. Zhao X, Fan Y, Vann PH, Wong JM, Sumien N, He JJ. Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging. Aging Dis. 2020;11:93–107.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Eugenin EA, King JE, Nath A, Calderon TM, Zukin RS, Bennett MVL, et al. HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci U S A. 2007;104:3438–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kruman II, Nath A, Mattson MP. HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp Neurol. 1998;154:276–88.

    Article  CAS  PubMed  Google Scholar 

  20. Paris JJ, Zou S, Hahn YK, Knapp PE, Hauser KF. 5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat. Brain Behav Immun. 2016;55:202–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Flora G, Pu H, Hennig B, Toborek M. Cyclooxygenase-2 is involved in HIV-1 Tat-induced inflammatory responses in the brain. Neuromolecular Med. 2006;8:337–52.

    Article  CAS  PubMed  Google Scholar 

  22. Mediouni S, Jablonski J, Paris JJ, Clementz MA, Thenin-Houssier S, McLaughlin JP, et al. Didehydro-cortistatin A inhibits HIV-1 Tat mediated neuroinflammation and prevents potentiation of cocaine reward in Tat transgenic mice. Curr HIV Res. 2015;13:64–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Paris JJ, Singh HD, Carey AN, McLaughlin JP. Exposure to HIV-1 Tat in brain impairs sensorimotor gating and activates microglia in limbic and extralimbic brain regions of male mice. Behav Brain Res. 2015;291:209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dickens AM, Yoo SW, Chin AC, Xu J, Johnson TP, Trout AL, et al. Chronic low-level expression of HIV-1 Tat promotes a neurodegenerative phenotype with aging. Sci Rep. 2017;7:7748.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Gonek M, McLane VD, Stevens DL, Lippold K, Akbarali HI, Knapp PE, et al. CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward. Brain Behav Immun. 2018;69:124–38.

    Article  CAS  PubMed  Google Scholar 

  26. Norman JP, Perry SW, Kasischke KA, Volsky DJ, Gelbard HA. HIV-1 trans activator of transcription protein elicits mitochondrial hyperpolarization and respiratory deficit, with dysregulation of complex IV and nicotinamide adenine dinucleotide homeostasis in cortical neurons. J Immunol. 2007;178:869–76.

    Article  CAS  PubMed  Google Scholar 

  27. Paris JJ, Liere P, Kim S, Mahdi F, Buchanan ME, Nass SR, et al. Pregnane steroidogenesis is altered by HIV-1 Tat and morphine: Physiological allopregnanolone is protective against neurotoxic and psychomotor effects. Neurobiol Stress. 2020;12:100211.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Sivalingam K, Cirino TJ, McLaughlin JP, Samikkannu T. HIV-Tat and Cocaine Impact Brain Energy Metabolism: Redox Modification and Mitochondrial Biogenesis Influence NRF Transcription-Mediated Neurodegeneration. Mol Neurobiol. 2020;58:490–504. https://doi.org/10.1007/s12035-020-02131-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schoenbaum EE, Hartel D, Lo Y, Howard AA, Floris-Moore M, Arnsten JH, et al. HIV infection, drug use, and onset of natural menopause. Clin Infect Dis. 2005;41:1517–24.

    Article  PubMed  Google Scholar 

  30. Fan MD, Maslow B-S, Santoro N, Schoenbaum E. HIV and the menopause. Menopause Int. 2008;14:163–8.

    Article  PubMed  Google Scholar 

  31. Karim R, Mack WJ, Kono N, Tien PC, Anastos K, Lazar J, et al. Gonadotropin and sex steroid levels in HIV-infected premenopausal women and their association with subclinical atherosclerosis in HIV-infected and -uninfected women in the women’s interagency HIV study (WIHS). J Clin Endocrinol Metab. 2013;98:E610–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Slama L, Jacobson LP, Li X, Palella FJ Jr, Margolick JB, Kingsley LA, et al. Longitudinal Changes Over 10 Years in Free Testosterone Among HIV-Infected and HIV-Uninfected Men. J Acquir Immune Defic Syndr. 2016;71:57–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ivanov AV, Valuev-Elliston VT, Ivanova ON, Kochetkov SN, Starodubova ES, Bartosch B, et al. Oxidative Stress during HIV Infection: Mechanisms and Consequences. Oxid Med Cell Longev. 2016;2016:8910396.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Fields JA, Ellis RJ. HIV in the cART era and the mitochondrial: immune interface in the CNS. Int Rev Neurobiol. 2019;145:29–65.

    Article  CAS  PubMed  Google Scholar 

  35. Mandas A, Iorio EL, Congiu MG, Balestrieri C, Mereu A, Cau D, et al. Oxidative imbalance in HIV-1 infected patients treated with antiretroviral therapy. J Biomed Biotechnol. 2009;2009:749575.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Manda KR, Banerjee A, Banks WA, Ercal N. Highly active antiretroviral therapy drug combination induces oxidative stress and mitochondrial dysfunction in immortalized human blood-brain barrier endothelial cells. Free Radic Biol Med. 2011;50:801–10.

    Article  CAS  PubMed  Google Scholar 

  37. Asundi A, Robles Y, Starr T, Landay A, Kinslow J, Ladner J, et al. Immunological and Neurometabolite Changes Associated With Switch From Efavirenz to an Integrase Inhibitor. J Acquir Immune Defic Syndr. 2019;81:585–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Duarte JMN, Do KQ, Gruetter R. Longitudinal neurochemical modifications in the aging mouse brain measured in vivo by 1H magnetic resonance spectroscopy. Neurobiol Aging. 2014;35:1660–8.

    Article  CAS  PubMed  Google Scholar 

  39. Carey AN, Liu X, Mintzopoulos D, Paris JJ, McLaughlin JP, Kaufman MJ. Conditional Tat protein brain expression in the GT-tg bigenic mouse induces cerebral fractional anisotropy abnormalities. Curr HIV Res. 2015;13:3–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hahn YK, Podhaizer EM, Farris SP, Miles MF, Hauser KF, Knapp PE. Effects of chronic HIV-1 Tat exposure in the CNS: heightened vulnerability of males versus females to changes in cell numbers, synaptic integrity, and behavior. Brain Struct Funct. 2015;220:605–23.

    Article  PubMed  Google Scholar 

  41. Schier CJ, Marks WD, Paris JJ, Barbour AJ, McLane VD, Maragos WF, et al. Selective Vulnerability of Striatal D2 versus D1 Dopamine Receptor-Expressing Medium Spiny Neurons in HIV-1 Tat Transgenic Male Mice. J Neurosci. 2017;37:5758–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zou S, Balinang JM, Paris JJ, Hauser KF, Fuss B, Knapp PE. Effects of HIV-1 Tat on oligodendrocyte viability are mediated by CaMKIIβ-GSK3β interactions. J Neurochem. 2019;149:98–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cirino TJ, Harden SW, McLaughlin JP, Frazier CJ. Region-specific effects of HIV-1 Tat on intrinsic electrophysiological properties of pyramidal neurons in mouse prefrontal cortex and hippocampus. J Neurophysiol. 2020;123:1332–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nass SR, Hahn YK, McLane VD, Varshneya NB, Damaj MI, Knapp PE, et al. Chronic HIV-1 Tat exposure alters anterior cingulate cortico-basal ganglia-thalamocortical synaptic circuitry, associated behavioral control, and immune regulation in male mice. Brain, Behavior, & Immunity - Health. 2020;5:100077.

    Article  Google Scholar 

  45. Strauss M, O’Donovan B, Ma Y, Xiao Z, Lin S, Bardo MT, et al. [3H]Dopamine Uptake through the Dopamine and Norepinephrine Transporters is Decreased in the Prefrontal Cortex of Transgenic Mice Expressing HIV-1 Transactivator of Transcription Protein. J Pharmacol Exp Ther. 2020;374:241–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kim BO, Liu Y, Ruan Y, Xu ZC, Schantz L, He JJ. Neuropathologies in transgenic mice expressing human immunodeficiency virus type 1 Tat protein under the regulation of the astrocyte-specific glial fibrillary acidic protein promoter and doxycycline. Am J Pathol. 2003;162:1693–707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Langford D, Oh Kim B, Zou W, Fan Y, Rahimain P, Liu Y, et al. Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model. J Neurovirol. 2018;24:168–79.

    Article  CAS  PubMed  Google Scholar 

  48. Paris JJ, Walf AA, Frye CA. II. Cognitive performance of middle-aged female rats is influenced by capacity to metabolize progesterone in the prefrontal cortex and hippocampus. Brain Res. 2011;1379:149–63.

    Article  CAS  PubMed  Google Scholar 

  49. Gruetter R. Automatic, localized in vivo adjustment of all first- and second-order shim coils. Magn Reson Med. 1993;29:804–11.

    Article  CAS  PubMed  Google Scholar 

  50. Tkac I, Starcuk Z, Choi I-Y, Gruetter R. In Vivo 1H NMR Spectroscopy of Rat Brain at 1 ms Echo Time. Magn Reson Med. 1999;41:649–56.

    Article  CAS  PubMed  Google Scholar 

  51. Deelchand DK, Van de Moortele P-F, Adriany G, Iltis I, Andersen P, Strupp JP, et al. In vivo 1H NMR spectroscopy of the human brain at 9.4 T: initial results. J Magn Reson. 2010;206:74–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82.

    Article  CAS  PubMed  Google Scholar 

  53. Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30:672–9.

    Article  CAS  PubMed  Google Scholar 

  54. Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed. 2001;14:260–4.

    Article  CAS  PubMed  Google Scholar 

  55. Henry P-G, Marjanska M, Walls JD, Valette J, Gruetter R, Ugurbil K. Proton-observed carbon-edited NMR spectroscopy in strongly coupled second-order spin systems. Magn Reson Med. 2006;55:250–7.

    Article  CAS  PubMed  Google Scholar 

  56. Walls AB, Waagepetersen HS, Bak LK, Schousboe A, Sonnewald U. The glutamine-glutamate/GABA cycle: function, regional differences in glutamate and GABA production and effects of interference with GABA metabolism. Neurochem Res. 2015;40:402–9.

    Article  CAS  PubMed  Google Scholar 

  57. Liu Y, Gu Y, Yu X. Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review. Quant Imaging Med Surg. 2017;7:707–26.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30:1–12.

    Article  CAS  PubMed  Google Scholar 

  59. Noble F, Rubira E, Boulanouar M, Palmier B, Plotkine M, Warnet J-M, et al. Acute systemic inflammation induces central mitochondrial damage and mnesic deficit in adult Swiss mice. Neurosci Lett. 2007;424:106–10.

    Article  CAS  PubMed  Google Scholar 

  60. Gavillet M, Allaman I, Magistretti PJ. Modulation of astrocytic metabolic phenotype by proinflammatory cytokines. Glia. 2008;56:975–89.

    Article  PubMed  Google Scholar 

  61. Chowdhury T, Allen MF, Thorn TL, He Y, Hewett SJ. Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production. Antioxidants (Basel). 2018;7. https://doi.org/10.3390/antiox7080100.

  62. Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol. 2013;94:1167–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Moosmann B, Behl C. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc Natl Acad Sci U S A. 1999;96:8867–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Dilek M, Naziroğlu M, Baha Oral H, Suat Ovey I, Küçükayaz M, Mungan MT, et al. Melatonin modulates hippocampus NMDA receptors, blood and brain oxidative stress levels in ovariectomized rats. J Membr Biol. 2010;233:135–42.

    Article  CAS  PubMed  Google Scholar 

  65. Da Silva MM, Schnorr CE, Behr GA, Gasparotto J, Bortolin RC, Moresco KS, et al. Oral administration of curcumin relieves behavioral alterations and oxidative stress in the frontal cortex, hippocampus, and striatum of ovariectomized Wistar rats. J Nutr Biochem. 2016;32:181–8.

    Article  CAS  Google Scholar 

  66. Yazğan B, Yazğan Y, Övey İS, Nazıroğlu M. Raloxifene and Tamoxifen Reduce PARP Activity, Cytokine and Oxidative Stress Levels in the Brain and Blood of Ovariectomized Rats. J Mol Neurosci. 2016;60:214–22.

    Article  PubMed  CAS  Google Scholar 

  67. Sárvári M, Hrabovszky E, Kalló I, Solymosi N, Tóth K, Likó I, et al. Estrogens regulate neuroinflammatory genes via estrogen receptors α and β in the frontal cortex of middle-aged female rats. J Neuroinflammation. 2011;8:82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Abbas AM, Elsamanoudy AZ. Effects of 17β-estradiol and antioxidant administration on oxidative stress and insulin resistance in ovariectomized rats. Can J Physiol Pharmacol. 2011;89:497–504.

    Article  PubMed  Google Scholar 

  69. Flora G, Lee YW, Nath A, Hennig B, Maragos W, Toborek M. Methamphetamine potentiates HIV-1 Tat protein-mediated activation of redox-sensitive pathways in discrete regions of the brain. Exp Neurol. 2003;179:60–70.

    Article  CAS  PubMed  Google Scholar 

  70. Banerjee A, Zhang X, Manda KR, Banks WA, Ercal N. HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: potential role of the thiol antioxidant N-acetylcysteine amide. Free Radic Biol Med. 2010;48:1388–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chivero ET, Guo M-L, Periyasamy P, Liao K, Callen SE, Buch S. HIV-1 Tat Primes and Activates Microglial NLRP3 Inflammasome-Mediated Neuroinflammation. J Neurosci. 2017;37:3599–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Menzie J, Pan C, Prentice H, Wu J-Y. Taurine and central nervous system disorders. Amino Acids. 2014;46:31–46.

    Article  CAS  PubMed  Google Scholar 

  73. Pasantes-Morales H. Taurine Homeostasis and Volume Control. Adv Neurobiol. 2017;16:33–53.

    Article  PubMed  Google Scholar 

  74. Jakaria M, Azam S, Haque ME, Jo S-H, Uddin MS, Kim I-S, et al. Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019;24:101223.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Benedetti MS, Russo A, Marrari P, Dostert P. Effects of ageing on the content in sulfur-containing amino acids in rat brain. J Neural Transm Gen Sect. 1991;86:191–203.

    Article  CAS  PubMed  Google Scholar 

  76. Shennan DB, Thomson J. Estrogen regulation and ion dependence of taurine uptake by MCF-7 human breast cancer cells. Cell Mol Biol Lett. 2007;12:396–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ritz M-F, Schmidt P, Mendelowitsch A. 17beta-estradiol effect on the extracellular concentration of amino acids in the glutamate excitotoxicity model in the rat. Neurochem Res. 2002;27:1677–83.

    Article  CAS  PubMed  Google Scholar 

  78. Dawson R Jr, Pelleymounter MA, Cullen MJ, Gollub M, Liu S. An age-related decline in striatal taurine is correlated with a loss of dopaminergic markers. Brain Res Bull. 1999;48:319–24.

    Article  CAS  PubMed  Google Scholar 

  79. El Idrissi A, Shen CH, L’amoreaux WJ. Neuroprotective role of taurine during aging. Amino Acids. 2013;45:735–50.

    Article  PubMed  CAS  Google Scholar 

  80. Chupel MU, Minuzzi LG, Furtado G, Santos ML, Hogervorst E, Filaire E, et al. Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women. Appl Physiol Nutr Metab. 2018;43:733–41.

    Article  CAS  PubMed  Google Scholar 

  81. Jeevanandam M, Young DH, Ramias L, Schiller WR. Effect of major trauma on plasma free amino acid concentrations in geriatric patients. Am J Clin Nutr. 1990;51:1040–5.

    Article  CAS  PubMed  Google Scholar 

  82. Paris JJ, Fenwick J, McLaughlin JP. Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS. Horm Behav. 2014;65:445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yoshino Y, Koga I, Wakabayashi Y, Kitazawa T, Ota Y. Prevalence of and Risk Factors for Low Free Testosterone Levels in Japanese Men with Well-controlled Human Immunodeficiency Virus Infection. Curr HIV Res. 2020;18:381–6.

    Article  CAS  PubMed  Google Scholar 

  84. De Vincentis S, Decaroli MC, Fanelli F, Diazzi C, Mezzullo M, Morini F, et al. Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV. Eur J Endocrinol. 2021;184:107–22.

    Article  PubMed  Google Scholar 

Download references

Availability of data and material

Data will be made available to qualified researchers upon request.

Funding

This work was supported in part by National Institutes of Health grants S10RR019356 (MJK), R01DA039044 (MJK and JPM), R00DA039791 (JJP), R01DA052851 (JJP), an administrative supplement from award P30GM122733 (JJP and MJK), and by the Counterdrug Technology Assessment Center, an office within the Office of National Drug Control Policy, via Contract No. DBK39-03-C-0075 (MJK), awarded by the Army Contracting Agency. The content of the information does not necessarily reflect the position or the policy of the U.S. Government, and no official endorsement should be inferred.

Author information

Authors and Affiliations

  1. Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA

    Jason J. Paris, Alaa N. Qrareya & Fakhri Mahdi

  2. McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA

    Xi Chen, Joseph Anderson, Fei Du & Marc J. Kaufman

  3. Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA

    Jay P. McLaughlin

Authors
  1. Jason J. Paris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alaa N. Qrareya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fakhri Mahdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fei Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jay P. McLaughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc J. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Drs. Paris and Kaufman conceptualized the study.

Drs. Chen, Du, and Ms. Qrareya, Mahdi, and Mr. Anderson acquired the data.

Drs. Paris, Chen, Du, and Kaufman, and Ms. Qrareya, Mahdi, and Mr. Anderson analyzed the data.

Drs. Paris, Du, and Kaufman interpreted the data.

Drs. Paris and Kaufman drafted the manuscript.

All authors reviewed, provided edits, and approved of the manuscript final version.

Corresponding author

Correspondence to Marc J. Kaufman.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

The animal research included in this study was conducted after review and approval by the McLean Hospital Institutional and Animal Care Use Committee (IACUC).

Additional information

Publisher’s note

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

Supplementary Information

Figure S1

Expression of tat mRNA via polymerase chain reaction. Expression of GAPDH and tat mRNA via PCR among aged male and female Tat-transgenic mice. In cases 1-19, the left band is GAPDH and the right band is tat in each case. In cases 20 and 21, the first two bands are GAPDH in each case and the second bands are tat in each case. (PNG 1166 kb)

High resolution image (TIFF 3167 kb)

ESM 1

(PDF 59 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paris, J.J., Chen, X., Anderson, J. et al. In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain. GeroScience 43, 1851–1862 (2021). https://doi.org/10.1007/s11357-021-00354-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-021-00354-w

Keywords

Search

Navigation