Abstract
Background and aims: In spite of the fact that GABA is a significant transmitter, little is known about the GABA system in aging, compared with other transmitter systems. [3H]tiagabine is a ligand for GABAergic neurons, which binds with 10-fold higher affinity to the GABA uptake site than [3H]nipecotic acid. The aim of this study was to study the binding of [3H]tiagabine to the GABA transporter 1, GAT-1, in human frontal cortex and cingulate cortex from individuals of varying ages. Methods: [3H]tiagabine binding experiments were conducted on post-mortem brain tissue from 19 individuals (age range 17–78 years) without known neurological or psychiatric disorders. Binding data vs age and postmortem interval was analysed by Pearson correlation. Results: The density of [3H]tiagabine binding to GAT-1 decreased significantly with increasing age in the frontal cortex, whereas binding affinity was unchanged. No significant alterations in binding parameters were observed in the cingulate cortex. No correlation was found between post-mortem delay and the number of [3H]tiagabine binding sites. Conclusions: According to the present study, presynaptical alterations in the GABA system are correlated with aging in the frontal cortex of the human brain. Further studies involving a broader range of brain regions seem warranted, to confirm the present findings and to enlarge knowledge about the GABA system in aging.
References
Ruano D, Araujo F, Bentareha R, Vitorica J. Age-related modifications on the GABAa receptor binding properties from Wistar rat prefrontal cortex. Brain Res 1996; 738: 103–8.
Araki T, Kato H, Fujiwara T, Itoyama Y. Regional age-related alterations in cholinergic and GABAergic receptors in the rat brain. Mech Ageing Dev 1996; 88: 49–60.
Ishige K. Age-related changes in [3H]baclofen binding in mouse cerebellum. Gen Pharmacol 1995; 26: 1229–35.
Cross JA, Cheetham SC, Crompton R, Katona CLE, Horton RW. Brain GABAb binding sites in depressed suicide victims. Psychiatry Res 1988; 26: 119–29.
Suhara T, Inoue O, Kobayashi K, Suzuki K, Itoh T, Tateno Y. No age-related changes in human benzodiazepine receptor binding measured by PET with [11C]Ro 15-4513. Neurosci Lett 1993; 159: 207–10.
Sundman I, Allard P, Eriksson A, Marcusson J. GABA uptake sites in suicide victims and in normal aging. Neuropsychobiol 1997; 35: 11–5.
Borden LA, Murali Dhar TG, Smith KE, Weinshank RL, Branchek TA, Gluchowski C. Tiagabine, SK&F 89976-A, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol 1994; 269: 219–24.
Durkin MM, Smith KE, Borden LA, Weinshank RL, Branchek TA, Gustafson EL. Localization of messenger RNAs encoding three GABA transporters in rat brain: an in situ hybridization study. Mol Brain Res 1995; 33: 7–21.
Swan M, Najlerahim A, Watson RE, Bennett JP. Distribution of mRNA for the GABA transporter GAT-1 in the rat brain: Evidence that GABA uptake is not limited to presynaptic neurons. J Anat 1994; 185: 315–23.
Minelli A, Brecha NC, Karschin C, DeBiasi S, Conti F. GAT-1, a high affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex. J Neurosci 1995; 15: 7734–46.
Sundman Eriksson I, Allard P, Marcusson J. [3H]Tiagabine binding to GABA uptake sites in human brain. Brain Res 1999; 851: 183–8.
Munson PJ, Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem 1980; 107: 220–39.
Andersson A, Sundman I, Marcusson J. Age stability of human brain 5-HT terminals studied with [3H]paroxetine binding. Gerontology 1992; 38: 127–32.
Arranz B, Eriksson A, Mellerup E, Plenge P, Marcusson J. Effect of aging in human cortical pre- and postsynaptic serotonin binding sites. Brain Res 1999; 620: 163–6.
Tejani-Butt SM, Ordway GA. Effect of age on [3H]nisoxetine binding to uptake sites for norepinephrine in the locus coeruleus of hu- mans. Brain Res 1992; 583: 312–5.
Allard P, Marcusson JO. Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen. Neurobi- ol Aging 1989; 10: 661–4.
De Keyser J, Ebinger G, Vauquelin G. Age-related changes in the human nigrostriatal dopaminergic system. Ann Neurol 1990; 27: 157–61.
Kemppainen N, Marjamaki P, Roytta M, Rinne JO. Different pat- tern of reduction of striatal dopamine reuptake sites in Alzheimer’s disease and ageing. J Neural Transm 2001; 108: 827–36.
Zelnik NJ, Angel I, Paul SM, Kleinman JE. Decreased density of human striatal dopamine uptake sites with age. Eur J Pharmacol 1986; 126: 175–6.
Beach TG, Walker R, McGeer EG. Patterns of gliosis in Alzheimer’s disease. Glia 1989; 2: 420–36.
Hansen LA, Armstrong DM, Terry RD. An immunohistochemi- cal quantification of fibrous atrocytes in the aging human cerebral cortex. Neurobiol Aging 1987; 8: 1–6.
Unger JW. Glial reaction in aging and Alzheimer’s disease. Mi- crosc Res Tech 1998; 43: 24–8.
Liu X, Erikson C, Brun A. Cortical synaptic changes and gliosis in normal aging, Alzheimer’s disease and frontal lobe degeneration. Dementia 1996; 7: 128–34.
Sundman I, Lernmark U, Marcusson J. [3H]nipecotic acid binding to GABA uptake sites in human brain. Brain Res 1992; 580: 311–6.
Suzdak PD, Foged C, Andersen KE. Quantitative autoradiographic characterization of the binding of [3H]tiagabine (NNC 05328) to the GABA uptake carrier. Brain Res 1994; 647: 231–41.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sundman-Eriksson, I., Allard, P. Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex. Aging Clin Exp Res 18, 257–260 (2006). https://doi.org/10.1007/BF03324657
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03324657