Age-related changes in GAD levels in the central auditory system of the rat

Changes in the levels of gamma-aminobutyric acid (GABA) are known to occur in different parts of the brain during aging. In our study we attempted to define the effect that aging has on glutamate decarboxylase (GAD), the key enzyme in the synthesis of GABA, in the central parts of the auditory system. Age-related changes in GAD65 and GAD67 levels were investigated using immunohistochemistry and Western blotting in the inferior colliculus (IC), the auditory cortex (AC) and the visual cortex in Long-Evans rats. The results show that aging is associated with a decrease in the numbers of GAD65- and 67-immunoreactive neurons and the optical density of their somas in both the IC and AC. Western blot analysis revealed a pronounced age-related decline in the levels of GAD65 and 67 proteins in both the IC and AC. For comparison, in the visual cortex the decrease in both proteins was less pronounced than in the IC and AC. A similar pattern of age-related changes was found in Fischer 344 rats, a strain that manifests a rapid loss of hearing function with aging. The observed age-related decline in the levels of GAD65 and 67 may contribute significantly to the deterioration of hearing function that accompanies aging in mammals, including man.

[1]  J. Brunso-Bechtold,et al.  Age‐related decline of presumptive inhibitory synapses in the sensorimotor cortex as revealed by the physical disector , 2001, The Journal of comparative neurology.

[2]  Jianning Wei,et al.  Post-translational Regulation of l-Glutamic Acid Decarboxylase in the Brain , 2008, Neurochemical Research.

[3]  R. Frisina.  Subcortical neural coding mechanisms for auditory temporal processing , 2001, Hearing Research.

[4]  J. Winer,et al.  Morphology of GABAergic neurons in the inferior colliculus of the cat , 1994, The Journal of comparative neurology.

[5]  E. Friedman,et al.  Temporal processing. , 1991, Journal of learning disabilities.

[6]  G. M. Gerken,et al.  Central tinnitus and lateral inhibition: an auditory brainstem model , 1996, Hearing Research.

[7]  D. Caspary,et al.  Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  Josef Syka,et al.  Auditory function in presbycusis: peripheral vs. central changes , 2003, Experimental Gerontology.

[9]  D. L. Martin,et al.  Regional distribution and relative amounts of glutamate decarboxylase isoforms in rat and mouse brain , 1999, Neurochemistry International.

[10]  J. Winer,et al.  Morphology and spatial distribution of GABAergic neurons in cat primary auditory cortex (AI) , 1994, The Journal of comparative neurology.

[11]  Pamela Souza,et al.  Aging alters the neural representation of speech cues , 2002, Neuroreport.

[12]  Josef Syka,et al.  Age-related changes in cochlear and brainstem auditory functions in Fischer 344 rats , 2006, Neurobiology of Aging.

[13]  Karl J. Zilles,et al.  The Cortex of the Rat: A Stereotaxic Atlas , 1985 .

[14]  D. Naritoku,et al.  Age-related changes in GABAA receptor subunit composition and function in rat auditory system , 1999, Neuroscience.

[15]  Josef Syka,et al.  Collagen changes in the cochlea of aged Fischer 344 rats , 2006, Experimental Gerontology.

[16]  A. Leventhal,et al.  GABA and Its Agonists Improved Visual Cortical Function in Senescent Monkeys , 2003, Science.

[17]  H J Gundersen,et al.  Pronounced loss of cell nuclei and anisotropic deformation of thick sections. , 1999, Journal of microscopy.

[18]  P. Dutar,et al.  Age-related alterations of GABAergic input to CA1 Pyramidal neurons and its control by nicotinic acetylcholine receptors in rat hippocampus , 2006, Neuroscience.

[19]  R. Batra,et al.  Monaural and binaural processing in the ventral nucleus of the lateral lemniscus: a major source of inhibition to the inferior colliculus , 2002, Hearing Research.

[20]  Sandra Gordon-Salant,et al.  Recognition of time-compressed and natural speech with selective temporal enhancements by young and elderly listeners. , 2007, Journal of speech, language, and hearing research : JSLHR.

[21]  A. Privat,et al.  Comparative distribution of GAD65 and GAD67 mRNAs and proteins in the rat spinal cord supports a differential regulation of these two glutamate decarboxylases in vivo , 1995, Journal of neuroscience research.

[22]  D. Diloreto,et al.  The influences of age, retinal topography, and gender on retinal degeneration in the Fischer 344 rat , 1994, Brain Research.

[23]  T M Mayhew,et al.  If you assume, you can make an ass out of u and me': a decade of the disector for stereological counting of particles in 3D space. , 1996, Journal of anatomy.

[24]  R J Salvi,et al.  Quantitative measures of hair cell loss in CBA and C57BL/6 mice throughout their life spans. , 1997, The Journal of the Acoustical Society of America.

[25]  Jeremy G. Turner,et al.  Divergent response properties of layer-V neurons in rat primary auditory cortex , 2005, Hearing Research.

[26]  D. Caspary,et al.  Alterations of GABAA receptor subunit mRNA levels in the aging Fischer 344 rat inferior colliculus , 1997, The Journal of comparative neurology.

[27]  H. Katsumaru,et al.  GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus , 1987, Brain Research.

[28]  W. O'Neill,et al.  Age-Related Alteration in Processing of Temporal Sound Features in the Auditory Midbrain of the CBA Mouse , 1998, The Journal of Neuroscience.

[29]  J. Syka,et al.  Auditory frequency and intensity discrimination in pigmented rats , 1996, Hearing Research.

[30]  A. Hendrickson,et al.  Differential localization of two glutamic acid decarboxylases (GAD65 and GAD67) in adult monkey visual cortex , 2004, The Journal of comparative neurology.

[31]  A. Leventhal,et al.  Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys , 2000, Nature Neuroscience.

[32]  C R Houser,et al.  Comparative localization of two forms of glutamic acid decarboxylase and their mRNAs in rat brain supports the concept of functional differences between the forms , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  L F Hughes,et al.  Age‐related synaptic changes in the central nucleus of the inferior colliculus of Fischer‐344 rats , 1999, The Journal of comparative neurology.

[34]  A. Gutiérrez,et al.  Age-related decrease of GABAA receptor subunits and glutamic acid decarboxylase in the rat inferior colliculus , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  E. G. Jones,et al.  Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  Larry F Hughes,et al.  Affects of aging on receptive fields in rat primary auditory cortex layer V neurons. , 2005, Journal of neurophysiology.

[37]  R. Felix,et al.  Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice , 2007, Hearing Research.

[38]  W. O'Neill,et al.  Age‐related changes in calbindin D‐28k and calretinin immunoreactivity in the inferior colliculus of CBA/CaJ and C57Bl/6 mice , 1997, The Journal of comparative neurology.

[39]  E. Lopez-Poveda,et al.  The inferior colliculus of the rat: Quantitative immunocytochemical study of GABA and glycine , 2005, Neuroscience.

[40]  M. Erlander,et al.  The structural and functional heterogeneity of glutamic acid decarboxylase: A review , 1991, Neurochemical Research.

[41]  Josef Syka,et al.  Cochlear function in young and adult Fischer 344 rats , 2003, Hearing Research.

[42]  Maintenance of inhibitory interneurons and boutons in sensorimotor cortex between middle and old age in Fischer 344 X Brown Norway rats , 2006, Journal of Chemical Neuroanatomy.

[43]  W. O'Neill,et al.  Early bilateral deafening prevents calretinin up-regulation in the dorsal cortex of the inferior colliculus of aged CBA/CaJ mice , 2001, Hearing Research.

[44]  S. Arneric,et al.  Age-related changes in brainstem auditory neurotransmitters: Measures of GABA and acetylcholine function , 1994, Hearing Research.

[45]  H. Schuknecht,et al.  Cochlear Pathology in Presbycusis , 1993, The Annals of otology, rhinology, and laryngology.

[46]  S. Gordon-Salant,et al.  Temporal factors and speech recognition performance in young and elderly listeners. , 1993, Journal of speech and hearing research.

[47]  J. Winer,et al.  Laminar distribution and neuronal targets of GABAergic axon terminals in cat primary auditory cortex (AI) , 1994, The Journal of comparative neurology.

[48]  O. Witte,et al.  Age-related decline of functional inhibition in rat cortex , 2010, Neurobiology of Aging.

[49]  Robert D Frisina,et al.  Speech recognition in noise and presbycusis: relations to possible neural mechanisms , 1997, Hearing Research.

[50]  F. D. Bilbao,et al.  Age-related changes in parvalbumin- and GABA-immunoreactive cells in the rat septum , 1995, Neurobiology of Aging.

[51]  Josef Syka,et al.  Aging cochleas in the F344 rat: Morphological and functional changes , 2007, Experimental Gerontology.

[52]  K. Parham,et al.  Distortion product otoacoustic emissions in the C57BL/6J mouse model of age-related hearing loss , 1997, Hearing Research.

[53]  D. L. Martin,et al.  Two isoforms of glutamate decarboxylase: why? , 1998, Trends in pharmacological sciences.

[54]  Xiangrui Li,et al.  Decreased proportion of GABA neurons accompanies age-related degradation of neuronal function in cat striate cortex , 2008, Brain Research Bulletin.

[55]  L. Hughes,et al.  Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex , 2005, Neuroscience.

[56]  M. Erlander,et al.  Different distributions of GAD65 and GAD67 mRNAS suggest that the two glutamate decarboxylases play distinctive functional roles , 1993, Journal of neuroscience research.

[57]  Henry Simon,et al.  Age-related alterations in the neural coding of envelope periodicities. , 2002, Journal of neurophysiology.

[58]  L. Hughes,et al.  Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system , 2008, Journal of Experimental Biology.

[59]  Y. Kubota,et al.  Neurochemical features and synaptic connections of large physiologically-identified GABAergic cells in the rat frontal cortex , 1998, Neuroscience.

[60]  M. Tuszynski,et al.  Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats , 2001, The Journal of comparative neurology.

[61]  I. Whishaw,et al.  Place and matching-to-place spatial learning affected by rat inbreeding (Dark–Agouti, Fischer 344) and albinism (Wistar, Sprague–Dawley) but not domestication (wild rat vs. Long–Evans, Fischer–Norway) , 2002, Behavioural Brain Research.

[62]  Claude Alain,et al.  Aging and the processing of sound duration in human auditory cortex , 2003, Hearing Research.

[63]  J. Syka,et al.  Changes in parvalbumin immunoreactivity with aging in the central auditory system of the rat , 2008, Experimental Gerontology.

[64]  R. Frisina,et al.  Age reduces response latency of mouse inferior colliculus neurons to AM sounds. , 2004, The Journal of the Acoustical Society of America.

[65]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[66]  Josef Syka,et al.  Plastic changes in the central auditory system after hearing loss, restoration of function, and during learning. , 2002, Physiological reviews.

[67]  G. Buzsáki,et al.  Inhibition and Brain Work , 2007, Neuron.

[68]  M. Erlander,et al.  Two genes encode distinct glutamate decarboxylases , 1991, Neuron.

[69]  Joseph W. Hall,et al.  Temporal processing deficits in the pre-senescent auditory system. , 2006, The Journal of the Acoustical Society of America.

[70]  D. Grantham,et al.  Temporal processing in the aging auditory system. , 1998, The Journal of the Acoustical Society of America.

[71]  Xiaoqin Wang,et al.  Neural representations of sinusoidal amplitude and frequency modulations in the primary auditory cortex of awake primates. , 2002, Journal of neurophysiology.

[72]  Ayla Ergün,et al.  Delayed inhibition in cortical receptive fields and the discrimination of complex stimuli. , 2005, Journal of neurophysiology.

[73]  A. Shetty,et al.  Aging in the rat hippocampus is associated with widespread reductions in the number of glutamate decarboxylase‐67 positive interneurons but not interneuron degeneration , 2004, Journal of neurochemistry.

[74]  D. Ruano,et al.  Rat hippocampal GABAergic molecular markers are differentially affected by ageing , 2003, Journal of neurochemistry.

[75]  H. Markram,et al.  Interneurons of the neocortical inhibitory system , 2004, Nature Reviews Neuroscience.

[76]  D. Turner,et al.  Hippocampal interneurons expressing glutamic acid decarboxylase and calcium‐binding proteins decrease with aging in Fischer 344 rats , 1998, The Journal of comparative neurology.

[77]  R. Albin,et al.  Age-related decrease in GABAB receptor binding in the Fischer 344 rat i inferior colliculus , 1994, Neurobiology of Aging.

[78]  M. Semple,et al.  Auditory temporal processing: responses to sinusoidally amplitude-modulated tones in the inferior colliculus. , 2000, Journal of neurophysiology.

[79]  H. Gundersen,et al.  Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator , 1991, The Anatomical record.

[80]  Gary W. Harding,et al.  The effect of an age-related hearing loss gene (Ahl) on noise-induced hearing loss and cochlear damage from low-frequency noise , 2005, Hearing Research.

[81]  A. Winseck,et al.  Stereological quantification of GAD‐67–immunoreactive neurons and boutons in the hippocampus of middle‐aged and old Fischer 344 × Brown Norway rats , 2004, The Journal of comparative neurology.

[82]  W. O'Neill,et al.  Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse , 1997, Journal of Comparative Physiology A.

[83]  D. Caspary,et al.  Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli. , 1996, Journal of neurophysiology.

[84]  Achim Klug,et al.  Roles of inhibition for transforming binaural properties in the brainstem auditory system , 2002, Hearing Research.

[85]  H. Markram,et al.  Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. , 2000, Science.

[86]  R. Helfert,et al.  Central auditory aging: GABA changes in the inferior colliculus , 1995, Experimental Gerontology.