Top

Published in:

01-10-2003 | Regular Paper

GluR2/3, NMDAε1 and GABA_A receptors in Creutzfeldt-Jakob disease

Authors: I. Ferrer, B. Puig

Published in: Acta Neuropathologica | Issue 4/2003

Abstract

The excitatory ionotropic glutamate receptors N-methyl-d-aspartate (NMDA) and α-amino-3-hydro-5methyl-4-isoxazole propionic acid (AMPA) receptors, and the inhibitory γ-aminobutyric acid (GABA) receptors are major regulators of synaptic transmission in the central nervous system. Glutamate receptors AMPA GluR2/3 and NMDA R2A: NR2A (NMDAε1), and GABA_A (GABA_A Rα1) receptors were examined by immunohistochemistry in the cerebral cortex (frontal cortex) entorhinal cortex, hippocampus and cerebellar cortex in nine patients with sporadic Creutzfeldt-Jakob disease (CJD) and eight age-matched controls obtained 3–8 h after death. All patients with CJD showed methionine/methionine in codon 129 of the prion protein gene. Decreased GluR2/3 immunoreactivity was found in the frontal cortex, entorhinal cortex and Purkinje cells; reduced NMDAε1 immunoreactivity was found in the frontal cortex, entorhinal cortex, and molecular and granular cell layers of the cerebellum. Decreased GluR2/3 and NMDAε1 immunoreactivity was also observed in the molecular layer of the dentate gyrus, but not in the hippocampus proper in cases with hippocampal involvement. GABA_A Rα1 expression was markedly decreased in the granular cell layer of the cerebellum in CJD. Decreased GluR2/3 and NMDAε1 expression correlated with prion protein deposition, neuron loss and spongiform degeneration in the cerebral cortex in every case. However, reduced GluR2/3 immunoreactivity in Purkinje cells was apparently independent of these parameters. In contrast to ionotropic glutamate receptors, GABA_A Rα1 immunoreactivity was moderately increased in the frontal cortex, entorhinal cortex and molecular layer of the cerebellum in CJD. The present results show marked and selective abnormalities in the expression of crucial neurotransmitter receptors in CJD, ionotropic glutamate receptors being more severely affected than ionotropic GABA receptors. These findings stress selective vulnerability of glutamate receptors versus GABA receptors in CJD.

Aguglia U, Oliveri RL, Gambardella A, Talerico G, Zappia M, De Sarro GB, Quattrone A (1996) Functional preservation of nezodiazepine receptors of the primary somatosensory cortex in Creutzfeldt-Jakob disease: a pharmacologic-evoked potential study. Clin Neuropharmacol 19:87–91PubMed

Barnard EA, Skolnick P, Olsen RW, Mohler H, Sieghart W, Biggio G, Braestrup C, Bateson AN, Langer SZ (1998) Subtypes of GABA_A receptors: classification on the basis of subunit structure and receptor function. Pharmacol Rev 50:291–313PubMed

Belichenko PV, Brown D, Jeffrey M, Fraser JR (2000) Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie-infected mice. Neuropathol Appl Neurobiol 26:143–149CrossRefPubMed

Bignami A, Parry HB (1972) Electron microscopic studies on the brain of sheep with natural scrapie. II. The small nerve processes in neuronal degeneration. Brain 95:487–494PubMed

Borges K, Digledine R (1998) AMPA receptors: molecular and functional diversity. Prog Brain Res 116:153–170PubMed

Brown D, Halliday W, Jeffrey M, Fraser J (1997) Visualising scrapie infected and normal neurons in the murine hippocampus using Golgi impregnation and confocal imaging of intracellular dye. J Cell Pathol 2:131–136

Brown DR, Herms JW, Schmidt B, Kretzschmar HA (1997) PrP and β amyloid fragments activate different neurotoxic mechanisms in cultured mouse cells. Eur J Neurosci 9:1162–1169PubMed

Catalá I, Ferrer I, Galofré E, Fábregues I (1988) Decreased numbers of dendritic spines on cortical pyramidal neurons in dementia. A quantitative Golgi study in biopsy samples. Hum Neurobiol 6:255–259PubMed

Chou SM, Payne WN, Gibbs CJ, Gajdusek DC (1980) Transmission and scanning electron microscopy of spongiform change in Creutzfeldt-Jakob disease. Brain 103:885–904PubMed

10.

Collinge J, Whittington MA, Sidle KCL, Smith J, Palmer MS, Clarke AR, Jeffreys JGR (1994) Prion protein is necessary for normal synaptic function. Nature 370:295–297PubMed

11.

Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7-61PubMed

12.

Ferrer I, Costa F, Grau Veciana JM (1981) Creutzfeldt-Jakob disease: a Golgi study. Neuropathol Appl Neurobiol 7:237–242PubMed

13.

Ferrer I, Casas R, Rivera R (1993) Parvalbumin-immunoreactive cortical neurons in Creutzfeldt-Jakob disease. Ann Neurol 34:864–866PubMed

14.

Gonatas NK, Terry RD, Weiss M (1965) Electron microscopic study in two cases of Jakob-Creutzfeldt disease. J Neuropathol Exp Neurol 24:575–598PubMed

15.

Güentchev M, Hainfellner JA, Trabattoni GR, Budka H (1997) Distribution of parvalbumin-immunoreactive neurons in brain correlates with hippocampal and temporal cortical pathology in Creutzfeldt-Jakob disease. J Neuropathol Exp Neurol 56:1119–1124

16.

Güentchev M, Groschup MH, Kodek R, Liberski PP, Budka H (1998) Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies. Brain Pathol 8:615–623PubMed

17.

Hogan RN, Baringer JR, Prusiner SB (1987) Scrapie infection diminishes spines and increases varicosities of dendrites in hamsters: a quantitative Golgi study. J Neuropathol Exp Neurol 46:461–473PubMed

18.

Hollmann M, Heinemann S (1994) Cloned glutamate receptors. Annu Rev Neurosci 17:31–108PubMed

19.

Ito Y, Amano T, Shimizu T, Hashimoto J, Kubo A, Fukuuchi Y (1998) Single-photon emission computed tomography image of benzodiazepine receptors in a patient with Creutzfeldt-Jakob disease. Intern Med 37:896–900PubMed

20.

Kannenberg K, Groschup MH, Siegel E (1995) Cellular prion protein and GABA_A receptors: no physical association? NeuroReport 7:77–80

21.

Korpi ER, Mattila MJ, Wisden W, Luddens H (1999) GABA_A-receptor subtypes: clinical efficiency and selectivity of benzodiazepine site ligands. Ann Med 29:275–282

22.

Lampert PW, Gajdusek DC, Gibbs CJ Jr (1971) Experimental spongiform encephalopathy (Creutzfeldt-Jakob disease) in chimpanzees. Electron microscopical studies. J Neuropathol Exp Neurol 30:20–32PubMed

23.

Landis DNMD, Williams RS, Masters CL (1981) Golgi and electron microscopic studies of spongiform encephalopathies. Neurology 31:538–549PubMed

24.

Liberski P, Yanigahira R, Asher DM, Gibbs CJ, Gajdusek DC (1990) Reevaluation of the ultrastructural pathology of experimental Creutzfeldt-Jakob disease. Brain 113:121–137PubMed

25.

Macdonald RL, Olsen RW (1994) GABA_A receptor channels. Annu Rev Neurosci 17:569–602PubMed

26.

Machado-Salas JP (1986) Dendritic and axonal spherules in the neocortex of a patient with Creutzfeldt-Jakob disease (CJD): Golgi and electron-microscopical investigation-neurobiological significance. Clin Neuropathol 5:176–184PubMed

27.

Marin O, Vial JD (1964) Neuropathological and ultrastructural findings in two cases of subacute spongiform encephalopathy. Acta Neuropathol 4:218–229

28.

Müller WEG, Ushijima H, Schröder HC, Forrest JM, Schatton WF, Rytik PG, Heffner-Lauc M (1993) Cytoprotective effect of NMDA receptor antagonists on prion protein (Prion^Sc)-induced toxicity in rat cortical cell cultures. Eur J Pharmacol 246:261–267CrossRefPubMed

29.

Nakanishi S, Nakajima Y, Masu M, Ueda Y, Ankara K, Watanaabe D, Yamaguchi S, Kawabata S, Okada M (1998) Glutamate receptors: brain function and signal transduction. Brain Res Rev 26:230–235CrossRefPubMed

30.

Olney JW, Ishimaru MJ (1999) Excitotoxic cell death. In: Koliatsos VE, Ratan RR (eds) Cell death and diseases of the nervous system. Humana Press, Totowa, pp 197–218

31.

Ozawa S, Kamiya H, Tsuzuki K (1998) Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 54:581–618PubMed

32.

Scallet AC, Ye X (1997) Excitotoxic mechanisms of neurodegeneration in transmissible spongiform encephalopathies. Ann NY Acad Sci 15:194–205

33.

Schoepfer R, Monyer H, Sommer B, Wisden W, Sprengel R, Kuner T, Lomeli H, Herb A, Kohler M, Burnashev N, Gunther W, Ruppersberg P, Seeburg P (1994) Molecular biology of glutamate receptors. Prog Neurobiol 42:353–357CrossRefPubMed

34.

Tateishi J, Sato Y, Ohta M (1983) Creutzfeldt-Jakob disease in humans and laboratory animals. Prog Neuropathol 5:195–221

35.

Wang Y, TesFaye E, Yasuda RP, Mash DC, Armstrong DM, Wolfe BB (2000) Effects of post-mortem delay on subunits of ionotropic glutamate receptors in human brain. Mol Brain Res 80:123–131CrossRefPubMed

36.

Yoneda Y, Kuramoto N, Kitayama T, Hinoi E (2001) Consolidation of transient ionotropic glutamate signals through nuclear transcription factors in the brain. Prog Neurobiol 63:697–719CrossRefPubMed

Title: GluR2/3, NMDAε1 and GABAA receptors in Creutzfeldt-Jakob disease
Authors: I. Ferrer
B. Puig
Publication date: 01-10-2003
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2003
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-003-0732-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GluR2/3, NMDAε1 and GABA_A receptors in Creutzfeldt-Jakob disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2003

Human ependymomas reveal frequent deletions on chromosomes 6 and 9

Variability and heterogeneity in Alzheimer's disease with cotton wool plaques: a clinicopathological study of four autopsy cases

Molecular characterization of desmosomes in meningiomas and arachnoidal tissue

Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study

Cerebral amyloid angiopathy in the elderly: vessel walls changes and relationship with dementia

Age-associated prevalence and risk factors of Lewy body pathology in a general population