β-Amyloid-induced apoptosis of cerebellar granule cells and cortical neurons: exacerbation by selective inhibition of group I metabotropic glutamate receptors

Administration of β-amyloid fragment 25–35 (Aβ 25–35) to cultured rat cerebellar granule cells (CGC) or cortical neurons caused cell death that was characterized by morphological and nuclear changes consistent with apoptosis. Inhibition of NMDA receptors produced a mild exacerbation of Aβ 25–35 toxi...

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Bibliographic Details
Published in:	Neuropharmacology Vol. 38; no. 8; pp. 1243 - 1252
Main Authors:	Allen, J.W, Eldadah, B.A, Faden, A.I
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-08-1999 Elsevier
Subjects:	AMPA/kainate receptor Amyloid beta-Peptides - toxicity Animals Apoptosis Biological and medical sciences Cells, Cultured Cerebellum - drug effects Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dizocilpine Maleate - pharmacology Excitatory Amino Acid Antagonists - pharmacology Medical sciences Metabotropic glutamate receptor Neocortex - drug effects Neocortex - physiopathology Neurology Neuronal death Neurons - drug effects Neurons - physiology NMDA receptor Peptide Fragments - toxicity Quinoxalines - pharmacology Rats Rats, Sprague-Dawley Receptors, Metabotropic Glutamate - drug effects β-Amyloid β-Amyloid Neuronal death AMPA/kainate receptor NMDA receptor Metabotropic glutamate receptor Apoptosis Cerebellum Ionotropic receptor Nervous system diseases Granule neuron Rat Alzheimer disease Pathogenesis Rodentia Central nervous system Molecular interaction Glutamate receptor In vitro Cerebral disorder Vertebrata Mammalia Metabotropic receptor Cell death β Amyloid protein Animal Central nervous system disease Degenerative disease Brain (vertebrata)
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Summary:	Administration of β-amyloid fragment 25–35 (Aβ 25–35) to cultured rat cerebellar granule cells (CGC) or cortical neurons caused cell death that was characterized by morphological and nuclear changes consistent with apoptosis. Inhibition of NMDA receptors produced a mild exacerbation of Aβ 25–35 toxicity in cortical neurons; a similar effect was induced by AMPA/kainate receptor inhibition in CGC. Selective activation of group I metabotropic glutamate receptors (mGluR) by dihyroxyphenylglycine (DHPG) had no effect on Aβ 25–35-induced apoptosis in either cell type, and was unaffected by blockade of ionotropic glutamate receptors. In contrast, selective inhibition of group I mGluR by ( RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) exacerbated Aβ toxicity in cortical neurons, whereas this treatment was without effect on CGC. However, AIDA significantly increased Aβ-induced apoptosis in CGC in the presence of either NMDA or AMPA/kainate receptor inhibition; blockade of both ionotropic glutamate receptor classes further increased the exacerbation of apoptosis following treatment with AIDA. These findings suggest that Aβ 25–35-induced neuronal injury leads to activation of group I mGluR, which attenuates the resulting apoptosis.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0028-3908 1873-7064
DOI:	10.1016/S0028-3908(99)00044-1