Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy

Fei Gao, Guangbin Wang, Wen Ma, Fuxin Ren, Muwei Li, Yuling Dong, Cheng Liu, Bo Liu, Xue Bai, Bin Zhao, Richard A E Edden, Fei Gao, Guangbin Wang, Wen Ma, Fuxin Ren, Muwei Li, Yuling Dong, Cheng Liu, Bo Liu, Xue Bai, Bin Zhao, Richard A E Edden

Abstract

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central auditory system. Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis. Edited magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, is the most widely used technique for detecting GABA in the human brain. However, to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis. In this study, sixteen patients with presbycusis (5 males/11 females, mean age 63.1 ± 2.6 years) and twenty healthy controls (6 males/14 females, mean age 62.5 ± 2.3 years) underwent audiological and MRS examinations. Pure tone audiometry from 0.125 to 8 kHz and tympanometry were used to assess the hearing abilities of all subjects. The pure tone average (PTA; the average of hearing thresholds at 0.5, 1, 2 and 4 kHz) was calculated. The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 × 3 × 3 cm(3) volumes centered on the left and right Heschl's gyri. GABA+ concentrations were significantly lower in the presbycusis group compared to the control group (left auditory regions: p = 0.002, right auditory regions: p = 0.008). Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group (r = -0.57, p = 0.02), while a similar trend was found in the control group (r = -0.40, p = 0.08). These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis and suggest a potential treatment target for presbycusis.

Copyright © 2014 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
The position of volumes of interest (4 × 3 × 3 cm3) in the right (above) and left auditory region (below) on sagittal (A, E) and coronal (B, F) T1-weighted images. The corresponding results of brain segmentation are shown for the right (C) and left auditory region (G). Representative GABA+-edited MEGA-PRESS spectra from the right auditory region (D) and the left auditory region (H) are shown.
Figure 2
Figure 2
Hearing thresholds of the presbycusis (PC) and normal control (NC) group as assessed using pure tone audiometry. Hearing thresholds from both ears are averaged. Data are shown as means ± standard deviation (SD) from 125 Hz to 8000 Hz (air conduction).
Figure 3
Figure 3
Correlations between pure tone average (PTA) and GABA+ concentrations in the presbycusis group (A), normal control group (B) and all subjects (C). A significant negative correlation was observed between PTA and GABA+ concentrations in the presbycusis group (r = −0.57, p = 0.02). A trend toward correlation was seen in the normal control group (r = −0.40, p = 0.08). A significant negative correlation was also observed between PTA and GABA+ concentrations in all subjects (r = −0.72, p

References

    1. Alvarado JC, Fuentes-Santamaria V, Gabaldon-Ull MC, Blanco JL, Juiz JM. Wistar rats: a forgotten model of age-related hearing loss. Front Aging Neurosci. 2014;6:29.
    1. Boy F, Evans CJ, Edden RA, Lawrence AD, Singh KD, Husain M, Sumner P. Dorsolateral prefrontal gamma-aminobutyric acid in men predicts individual differences in rash impulsivity. Biol Psychiatry. 2011;70:866–872.
    1. Burianova J, Ouda L, Profant O, Syka J. Age-related changes in GAD levels in the central auditory system of the rat. Experimental Gerontology. 2009;44:161–169.
    1. Caspary DM, Holder TM, Hughes LF, Milbrandt JC, McKernan RM, Naritoku DK. Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system. Neuroscience. 1999;93:307–312.
    1. Caspary DM, Hughes LF, Ling LL. Age-related GABAA receptor changes in rat auditory cortex. Neurobiology of Aging. 2013;34:1486–1496.
    1. Caspary DM, Milbrandt JC, Helfert RH. Central auditory aging: GABA changes in the inferior colliculus. Exp Gerontol. 1995;30:349–360.
    1. Caspary DM, Raza A, Lawhorn Armour BA, Pippin J, Arneric SP. Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis. J Neurosci. 1990;10:2363–2372.
    1. Edden RA, Crocetti D, Zhu H, Gilbert D, Mostofsky S. Reduced GABA concentration in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2012a;69:750–753.
    1. Edden RA, Intrapiromkul J, Zhu H, Cheng Y, Barker PB. Measuring T2 in vivo with J-difference editing: application to GABA at 3 Tesla. J Magn Reson Imaging. 2012b;35:229–234.
    1. Edden RA, Muthukumaraswamy SD, Freeman TC, Singh KD. Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex. J Neurosci. 2009;29:15721–15726.
    1. Edden RA, Puts NA, Barker PB. Macromolecule-suppressed GABA-edited magnetic resonance spectroscopy at 3T. Magn Reson Med. 2012c;68:657–661.
    1. Edden RAE, Puts NAJ, Harris AD, Barker PB, Evans CJ. Gannet: A batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra. Journal of Magnetic Resonance Imaging. 2013 doi: 10.1002/jmri.24478.
    1. Foerster BR, Pomper MG, Callaghan BC, Petrou M, Edden RAE, Mohamed MA, Welsh RC, Carlos RC, Barker PB, Feldman EL. An Imbalance Between Excitatory and Inhibitory Neurotransmitters in Amyotrophic Lateral Sclerosis Revealed by Use of 3-T Proton Magnetic Resonance Spectroscopy. JAMA Neurology. 2013;70:1009.
    1. Gao F, Edden RA, Li M, Puts NA, Wang G, Liu C, Zhao B, Wang H, Bai X, Zhao C, Wang X, Barker PB. Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels. Neuroimage. 2013;78:75–82.
    1. Gasparovic C, Song T, Devier D, Bockholt HJ, Caprihan A, Mullins PG, Posse S, Jung RE, Morrison LA. Use of tissue water as a concentration reference for proton spectroscopic imaging. Magn Reson Med. 2006;55:1219–1226.
    1. Gordon-Salant S, Fitzgibbons PJ. Temporal factors and speech recognition performance in young and elderly listeners. J Speech Hear Res. 1993;36:1276–1285.
    1. Gordon-Salant S, Fitzgibbons PJ, Friedman SA. Recognition of time-compressed and natural speech with selective temporal enhancements by young and elderly listeners. J Speech Lang Hear Res. 2007;50:1181–1193.
    1. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 2000;13:129–153.
    1. Ito J, Sakakibara J, Honjo I, Iwasaki Y, Yonekura Y. Positron emission tomographic study of auditory sensation in a patient with a cochlear implant. Arch Otolaryngol Head Neck Surg. 1990;116:1437–1439.
    1. Ito J, Sakakibara J, Iwasaki Y, Yonekura Y. Positron emission tomography of auditory sensation in deaf patients and patients with cochlear implants. Ann Otol Rhinol Laryngol. 1993;102:797–801.
    1. Kwon SH, Scheinost D, Lacadie C, Benjamin J, Myers EH, Qiu M, Schneider KC, Rothman DL, Constable RT, Ment LR. GABA, Resting-State Connectivity and the Developing Brain. Neonatology. 2014;106:149–155.
    1. Lin FR, Thorpe R, Gordon-Salant S, Ferrucci L. Hearing loss prevalence and risk factors among older adults in the United States. J Gerontol A Biol Sci Med Sci. 2011;66:582–590.
    1. Ling LL, Hughes LF, Caspary DM. Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex. Neuroscience. 2005;132:1103–1113.
    1. Litovsky RY, Delgutte B. Neural correlates of the precedence effect in the inferior colliculus: effect of localization cues. J Neurophysiol. 2002;87:976–994.
    1. Lu H, Nagae-Poetscher LM, Golay X, Lin D, Pomper M, van Zijl PC. Routine clinical brain MRI sequences for use at 3.0 Tesla. J Magn Reson Imaging. 2005;22:13–22.
    1. Marenco S, Savostyanova AA, van der Veen JW, Geramita M, Stern A, Barnett AS, Kolachana B, Radulescu E, Zhang F, Callicott JH, Straub RE, Shen J, Weinberger DR. Genetic modulation of GABA levels in the anterior cingulate cortex by GAD1 and COMT. Neuropsychopharmacology. 2010;35:1708–1717.
    1. Mazelova J, Popelar J, Syka J. Auditory function in presbycusis: peripheral vs. central changes. Exp Gerontol. 2003;38:87–94.
    1. Mescher M, Merkle H, Kirsch J, Garwood M, Gruetter R. Simultaneous in vivo spectral editing and water suppression. NMR Biomed. 1998;11:266–272.
    1. Montelius M, et al. ESMRMB. 2008. Oct 1–3, MATLAB tool for segmentation and re-creation of 1H-MRS volumes of interest in MRI image stacks. Antalya/TR.
    1. Mullins PG, McGonigle DJ, O’Gorman RL, Puts NA, Vidyasagar R, Evans CJ, Edden RA. Current practice in the use of MEGA-PRESS spectroscopy for the detection of GABA. Neuroimage. 2014;86:43–52.
    1. Narayan R, Ergun A, Sen K. Delayed inhibition in cortical receptive fields and the discrimination of complex stimuli. J Neurophysiol. 2005;94:2970–2975.
    1. Ouda L, Druga R, Syka J. Changes in parvalbumin immunoreactivity with aging in the central auditory system of the rat. Experimental Gerontology. 2008;43:782–789.
    1. Ouda L, Syka J. Immunocytochemical profiles of inferior colliculus neurons in the rat and their changes with aging. Front Neural Circuits. 2012;6:68.
    1. Palombi PS, Caspary DM. Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli. J Neurophysiol. 1996;76:3114–3125.
    1. Pecka M, Zahn TP, Saunier-Rebori B, Siveke I, Felmy F, Wiegrebe L, Klug A, Pollak GD, Grothe B. Inhibiting the inhibition: a neuronal network for sound localization in reverberant environments. J Neurosci. 2007;27:1782–1790.
    1. Piechnik SK, Evans J, Bary LH, Wise RG, Jezzard P. Functional changes in CSF volume estimated using measurement of water T2 relaxation. Magn Reson Med. 2009;61:579–586.
    1. Profant O, Balogova Z, Dezortova M, Wagnerova D, Hajek M, Syka J. Metabolic changes in the auditory cortex in presbycusis demonstrated by MR spectroscopy. Exp Gerontol. 2013;48:795–800.
    1. Puts NA, Barker PB, Edden RA. Measuring the longitudinal relaxation time of GABA in vivo at 3 Tesla. J Magn Reson Imaging. 2013;37:999–1003.
    1. Puts NA, Edden RA. In vivo magnetic resonance spectroscopy of GABA: a methodological review. Prog Nucl Magn Reson Spectrosc. 2012;60:29–41.
    1. Puts NA, Edden RA, Evans CJ, McGlone F, McGonigle DJ. Regionally specific human GABA concentration correlates with tactile discrimination thresholds. J Neurosci. 2011;31:16556–16560.
    1. Raza A, Milbrandt JC, Arneric SP, Caspary DM. Age-related changes in brainstem auditory neurotransmitters: measures of GABA and acetylcholine function. Hear Res. 1994;77:221–230.
    1. Rojas DC, Teale P, Sheeder J, Simon J, Reite M. Sex-specific expression of Heschl’s gyrus functional and structural abnormalities in paranoid schizophrenia. Am J Psychiatry. 1997;154:1655–1662.
    1. Rothman DL, Behar KL, Prichard JW, Petroff OA. Homocarnosine and the measurement of neuronal pH in patients with epilepsy. Magn Reson Med. 1997;38:924–929.
    1. Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A. 1993;90:5662–5666.
    1. Rowland LM, Edden RA, Kontson K, Zhu H, Barker PB, Hong LE. GABA predicts inhibition of frequency-specific oscillations in schizophrenia. J Neuropsychiatry Clin Neurosci. 2013;25:83–87.
    1. Snell KB, Frisina DR. Relationships among age-related differences in gap detection and word recognition. J Acoust Soc Am. 2000;107:1615–1626.
    1. Stagg CJ, Bachtiar V, Johansen-Berg H. What are we measuring with GABA magnetic resonance spectroscopy? Commun Integr Biol. 2011;4:573–575.
    1. Syka J. The Fischer 344 rat as a model of presbycusis. Hear Res. 2010;264:70–78.
    1. Tang X, Zhu X, Ding B, Walton JP, Frisina RD, Su J. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse. Neuroscience. 2014;259:184–193.
    1. Van Eyken E, Van Laer L, Fransen E, Topsakal V, Lemkens N, Laureys W, Nelissen N, Vandevelde A, Wienker T, Van De Heyning P, Van Camp G. KCNQ4: a gene for age-related hearing impairment? Hum Mutat. 2006;27:1007–1016.
    1. Walton JP, Simon H, Frisina RD. Age-related alterations in the neural coding of envelope periodicities. J Neurophysiol. 2002;88:565–578.
    1. Wansapura JP, Holland SK, Dunn RS, Ball WS., Jr NMR relaxation times in the human brain at 3.0 tesla. J Magn Reson Imaging. 1999;9:531–538.
    1. Zhang Y, Brady M, Smith S. Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging. 2001;20:45–57.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren