Summary
Binding of [3 H]D-aspartate, as an indicator of glutamate uptake sites, was investigated in post-mortem human brain tissue by use of a centrifugation assay to separate free and bound ligand. Binding was displaceable, apparently saturable and to a single site, with mean KD and Bmax values of 2.3 μM and 40.3 nmol/g tissue in the frontal cortex. The method was applied to the study of tissue from frontal and temporal cortices and the caudate nucleus of five psychiatric patients who had undergone a frontal leucotomy. The effects of this neurosurgical procedure were to diminish by almost 50% the density of D-aspartate binding sites in the frontal cortex and caudate nucleus, while the temporal cortex was less affected. It is concluded that the method provides a potentially useful correlate of glutamatergic innervation in human brain tissue.
References
Anderson KJ, Bridges RJ, Cotman CW (1991) Increased density of excitatory amino acid transport sites in the hippocampal formation following an entorhinal lesion. Brain Res 562: 285–290
Bennet JPJr, Logan WJ, Snyder SW (1973) Amino acids as central nervous transmitters. The influence of ions, amino acid analogues and ontogeny on transport systems for L-glutamic and L-aspartic acids into central nervous synaptosomes of the rat. J Neurochem 21: 1533–1550
Carlsson M, Carlsson A (1990) Schizophrenia: a subcortical neurotransmitter imbalance syndrome? Schizophr Bull 16: 425–432
Cross AJ, Skan WJ, Slater P (1986) The association of [3H]D-aspartate binding and highaffinity glutamate uptake in human brain. Neurosci Lett 63: 12
Cross AJ, Slater P, Candy JM, Perry EK, Perry EH (1987) Glutamate deficits in Alzheimer's disease. J Neurol Neurosurg Psychiatry 50: 357–358
Czudek C, Reynolds GP (1990) [3H]Nipecotic acid binding to GABA uptake sites in postmortem human brain. J Neurochem 55: 165–168
Danbolt NC, Storm-Mathisen J (1986) Na+ dependant “binding“ of D-aspartate in brain membranes is largley due to uptake into membrane-bounded saccules. J Neurochem 47: 819–824
Fonnum F (1984) Glutamate: a neurotransmitter in mammalian brain. J Neurochem 42: 1–11
Greenamyre JT, Penney JB, Young AB, D'Amato CJ, Hicks SP, Shoulson I (1985) Alterations in L-glutamate binding in Alzheimer's and Huntington's diseases. Science 227: 1496–1499
Hardy JA, Cowburn R, Barton A, Reynolds GP, Lofdahl E, Carroll A-M, Wester P, Winblad B (1987) Glutamate deficits in Alzheimer's disease. J Neurol Neurosurg Psychiatry 50: 356–357
Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis of schizophrenia. Neurosci Lett 20: 379–382
Ogita K, Yoneda Y (1986) Characterization of Na +-dependant binding sites of [3H]glutamate in synaptic membranes from rat brain. Brain Res 397: 137–144
Reynolds GP, Pearson SJ (1987) Decreased glutamate and increased serotonin in Huntington's disease. Neurosci Lett 78: 233–238
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cutts, A.J., Reynolds, G.P. D-aspartate binding to the glutamate uptake site in human brain tissue — effects of leucotomy. J. Neural Transmission 94, 147–152 (1993). https://doi.org/10.1007/BF01245008
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01245008