FENS Forum 2006

FENS Forum 2006 - Vienna

For lectures, symposia and workshops, time indicates the beginning of the session.
For posters, authors are expected to be in attendance at their posters at the time indicated.

First author: Albasanz, José Luis (poster)

Poster board 439 - Tue 11/07, 12:15 - Hall Y
Session 162 - Alzheimer's disease III
Abstract A162.2, published in FENS Forum Abstracts, vol. 3, 2006.
Ref.: FENS Abstr., vol.3, A162.2, 2006

Author(s) Albasanz J. L. (1), Dalfó E. (2), Ferrer I. (2, 3) & Martín M. (1).

Addresse(s) (1) Dept. Inor. Org. Bioq. Facultad Quimicas, Ciudad Real, Spain; (2) Dept. Biol Cel. y Anat. Pat. Fac. Medicina, Barcelona, Spain; (3) Inst. Neuropatol. Hosp. Bellvitge, Barcelona, Spain.

Title Metabotropic glutamate receptors are decreased and desensitized in the cerebral cortex in Alzheimer's disease and common form of dementia with lewy bodies.

Text Glutamate is the main excitatory neurotransmitter in the CNS which is involved in learning and memory processes through ionotropic and metabotropic receptors. At high concentration glutamate acts as an excitotoxin producing degeneration and neuronal death. Dementia with Lewy Bodies (DLB) is a primary neurodegenerative disease with clinical and pathological characteristics of both Parkinson’s disease (PD) and Alzheimer’s disease (AD). Changes characteristic of AD, including senile plaques and neurofibrillary tangles, are also present in many patients with DLB. Cases with no or with minor AD-related associated changes are considered pure forms of DLB, whereas cases with marked AD-related pathology are considered common forms of DLB (cDLB). The aim of the present work was to analyze the status of metabotropic glutamate receptors (mGluRs) in the frontal cortex from cases with common form DLB and pure AD in comparison with age-matched controls. mGluRs, determined by radioligand binding assays, were significantly decreased in cDLB. This decrease correlated with AD neuropathological changes, at its greatest in isocortical stages, which was associated with a decrease in the expression levels of mGluR1 detected by Western blotting. Moreover, mGluRs analyzed in pure AD were lower than those obtained in cDLB and also correlated with progression of illness. Phospholipase Cbeta1 (PLCbeta1) isoform, which is the effector system of group I mGluRs, was decreased in parallel in cDLB cases. PLCbeta1 decrease was associated with reduced 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. In contrasts, mGluRs are increased in pure form of DLB. Therefore, mGluRs dysfunction may be implicated in the pathogenesis of cognitive impairment and dementia in common form of DLB and pure AD.

Theme Neurological and psychiatric conditions
Neurodegenerative disorders / Alzheimers disease: Neuropharmacology and neurotransmitters

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Author(s)	Albasanz J. L. (1), Dalfó E. (2), Ferrer I. (2, 3) & Martín M. (1).
Addresse(s)	(1) Dept. Inor. Org. Bioq. Facultad Quimicas, Ciudad Real, Spain; (2) Dept. Biol Cel. y Anat. Pat. Fac. Medicina, Barcelona, Spain; (3) Inst. Neuropatol. Hosp. Bellvitge, Barcelona, Spain.
Title	Metabotropic glutamate receptors are decreased and desensitized in the cerebral cortex in Alzheimer's disease and common form of dementia with lewy bodies.
Text	Glutamate is the main excitatory neurotransmitter in the CNS which is involved in learning and memory processes through ionotropic and metabotropic receptors. At high concentration glutamate acts as an excitotoxin producing degeneration and neuronal death. Dementia with Lewy Bodies (DLB) is a primary neurodegenerative disease with clinical and pathological characteristics of both Parkinson’s disease (PD) and Alzheimer’s disease (AD). Changes characteristic of AD, including senile plaques and neurofibrillary tangles, are also present in many patients with DLB. Cases with no or with minor AD-related associated changes are considered pure forms of DLB, whereas cases with marked AD-related pathology are considered common forms of DLB (cDLB). The aim of the present work was to analyze the status of metabotropic glutamate receptors (mGluRs) in the frontal cortex from cases with common form DLB and pure AD in comparison with age-matched controls. mGluRs, determined by radioligand binding assays, were significantly decreased in cDLB. This decrease correlated with AD neuropathological changes, at its greatest in isocortical stages, which was associated with a decrease in the expression levels of mGluR1 detected by Western blotting. Moreover, mGluRs analyzed in pure AD were lower than those obtained in cDLB and also correlated with progression of illness. Phospholipase Cbeta1 (PLCbeta1) isoform, which is the effector system of group I mGluRs, was decreased in parallel in cDLB cases. PLCbeta1 decrease was associated with reduced 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. In contrasts, mGluRs are increased in pure form of DLB. Therefore, mGluRs dysfunction may be implicated in the pathogenesis of cognitive impairment and dementia in common form of DLB and pure AD.
Theme	Neurological and psychiatric conditions Neurodegenerative disorders / Alzheimers disease: Neuropharmacology and neurotransmitters