Journal
NEUROBIOLOGY OF DISEASE
Volume 20, Issue 3, Pages 685-693Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.05.001
Keywords
dementia with Lewy bodies; Alzheimer's disease; metabotropic glutamate receptor; phospholipase C
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The aim of the present work was to analyze the status of metabotropic glutamate receptors (mGluRs) in the frontal cortex (area 8) from ten cases with common form DLB (eDLB) and eleven cases with pure AD in comparison with five age-matched controls. mGluRs, determined by radioligand binding assays, were significantly decreased in cerebral cortex in eDLB. This decrease was already present in cases with early AD changes not involving the frontal cortex, but dramatically correlated with AD neuropathological changes, at its greatest in isocortical stages, which was associated with a decrease in the expression levels of mGluR(I) detected by Western blotting. Moreover, mGluRs analyzed in pure AD were lower than those obtained in cDLB and also correlated with progression of illness. On the other hand, the expression levels of phospholipase C beta(1) (PLC beta(1)) isoform, which is the effector of group I mGluRs, was decreased in parallel in cDLB cases. Finally, the PLC beta(1) decrease was associated with reduced GTP- and L-glutamate-stimulated PLC activity in both cDLB and AD cases. These results show that group I mGluRs/PLC signaling are down-regulated and desensitized in the frontal cortex in cDLB and AD cases and that these modifications worsen with progression of AD changes in the cerebral neocortex. Therefore, group I mGluR dysfunction may be implicated in the pathogenesis of cognitive impairment and dementia in common form of DLB and pure AD. (c) 2005 Elsevier Inc. All rights reserved.
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