The mRNA of the NR1 subtype of glutamate receptor in Alzheimer's disease

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Abstract

Glutamate has been implicated in the pathogenesis of Alzheimer's disease (AD). Controversial data exists regarding changes in the N-methyl-D-aspartate (NMDA) receptor complex in AD. We wished to elucidate the hypothesis that the NMDA receptor system is involved in the pathogenesis of AD using a gene expression approach targeting the mRNA of the universal subtype of the NMDA receptor NR1. This was performed using in situ hybridization and antisense 35S-labelled oligonucleotides on brain tissue collected at post-mortem. Relative mRNA expression was measured in standardised optical density units (OD units) using videodensitometry without knowledge of the diagnosis. The study population consisted of AD (n = 6) and neurodegenerative non-Alzheimer controls (non-AD, n = 14). Gene expression was measured in the frontal lobe, superior temporal gyrus and three areas within the hippocampus. We have observed no significant differences in the relative mRNA expression of the NR1 subtype of glutamate receptor in the following regions: frontal lobe AD = 60.7 +/- 14.1 OD units mRNA (x +/- 1SE) vs 52.6 +/- 1 in non-AD (Mann-Whitney test, p = 0.477); the superior temporal gyrus: AD = 53.3 +/- 13.9 vs 38.2 +/- 7 (p = 0.37); the CA1 region: AD = 37.8 +/- 7.75 vs 81.5 +/- 25.7 (p = 0.66); subiculum AD = 46.7 +/- 11.0 vs 105 +/- 43.3 (p = 0.82); parahippocampal gyrus AD = 36.6 +/- 9.3 vs 81.7 +/- 40.6 (p = 0.90). There were trends to a reduction in NR1 mRNA in the hippocampus and increased NR1 within the frontal and superficial temporal gyrus which were not significant. There was variation within and between all patients with and without AD in the magnitude of NR1 expression in all anatomical regions studied. The findings suggest heterogeneity in the involvement of the post-synaptic glutamatergic system in AD.

Original languageEnglish
Pages (from-to)77-89
Number of pages13
JournalJournal of Neural Transmission
Volume109
Issue number1
DOIs
Publication statusPublished - 2002

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Glutamate Receptors
Alzheimer Disease
Messenger RNA
Temporal Lobe
N-Methyl-D-Aspartate Receptors
Hippocampus
Frontal Lobe
Gene Expression
Parahippocampal Gyrus
Oligonucleotides
In Situ Hybridization
Glutamic Acid

Cite this

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title = "The mRNA of the NR1 subtype of glutamate receptor in Alzheimer's disease",
abstract = "Glutamate has been implicated in the pathogenesis of Alzheimer's disease (AD). Controversial data exists regarding changes in the N-methyl-D-aspartate (NMDA) receptor complex in AD. We wished to elucidate the hypothesis that the NMDA receptor system is involved in the pathogenesis of AD using a gene expression approach targeting the mRNA of the universal subtype of the NMDA receptor NR1. This was performed using in situ hybridization and antisense 35S-labelled oligonucleotides on brain tissue collected at post-mortem. Relative mRNA expression was measured in standardised optical density units (OD units) using videodensitometry without knowledge of the diagnosis. The study population consisted of AD (n = 6) and neurodegenerative non-Alzheimer controls (non-AD, n = 14). Gene expression was measured in the frontal lobe, superior temporal gyrus and three areas within the hippocampus. We have observed no significant differences in the relative mRNA expression of the NR1 subtype of glutamate receptor in the following regions: frontal lobe AD = 60.7 +/- 14.1 OD units mRNA (x +/- 1SE) vs 52.6 +/- 1 in non-AD (Mann-Whitney test, p = 0.477); the superior temporal gyrus: AD = 53.3 +/- 13.9 vs 38.2 +/- 7 (p = 0.37); the CA1 region: AD = 37.8 +/- 7.75 vs 81.5 +/- 25.7 (p = 0.66); subiculum AD = 46.7 +/- 11.0 vs 105 +/- 43.3 (p = 0.82); parahippocampal gyrus AD = 36.6 +/- 9.3 vs 81.7 +/- 40.6 (p = 0.90). There were trends to a reduction in NR1 mRNA in the hippocampus and increased NR1 within the frontal and superficial temporal gyrus which were not significant. There was variation within and between all patients with and without AD in the magnitude of NR1 expression in all anatomical regions studied. The findings suggest heterogeneity in the involvement of the post-synaptic glutamatergic system in AD.",
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author = "Panegyres, {P K} and K Zafiris-Toufexis and Kakulas, {B A}",
year = "2002",
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journal = "Journal of Neural Transmission",
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T1 - The mRNA of the NR1 subtype of glutamate receptor in Alzheimer's disease

AU - Panegyres, P K

AU - Zafiris-Toufexis, K

AU - Kakulas, B A

PY - 2002

Y1 - 2002

N2 - Glutamate has been implicated in the pathogenesis of Alzheimer's disease (AD). Controversial data exists regarding changes in the N-methyl-D-aspartate (NMDA) receptor complex in AD. We wished to elucidate the hypothesis that the NMDA receptor system is involved in the pathogenesis of AD using a gene expression approach targeting the mRNA of the universal subtype of the NMDA receptor NR1. This was performed using in situ hybridization and antisense 35S-labelled oligonucleotides on brain tissue collected at post-mortem. Relative mRNA expression was measured in standardised optical density units (OD units) using videodensitometry without knowledge of the diagnosis. The study population consisted of AD (n = 6) and neurodegenerative non-Alzheimer controls (non-AD, n = 14). Gene expression was measured in the frontal lobe, superior temporal gyrus and three areas within the hippocampus. We have observed no significant differences in the relative mRNA expression of the NR1 subtype of glutamate receptor in the following regions: frontal lobe AD = 60.7 +/- 14.1 OD units mRNA (x +/- 1SE) vs 52.6 +/- 1 in non-AD (Mann-Whitney test, p = 0.477); the superior temporal gyrus: AD = 53.3 +/- 13.9 vs 38.2 +/- 7 (p = 0.37); the CA1 region: AD = 37.8 +/- 7.75 vs 81.5 +/- 25.7 (p = 0.66); subiculum AD = 46.7 +/- 11.0 vs 105 +/- 43.3 (p = 0.82); parahippocampal gyrus AD = 36.6 +/- 9.3 vs 81.7 +/- 40.6 (p = 0.90). There were trends to a reduction in NR1 mRNA in the hippocampus and increased NR1 within the frontal and superficial temporal gyrus which were not significant. There was variation within and between all patients with and without AD in the magnitude of NR1 expression in all anatomical regions studied. The findings suggest heterogeneity in the involvement of the post-synaptic glutamatergic system in AD.

AB - Glutamate has been implicated in the pathogenesis of Alzheimer's disease (AD). Controversial data exists regarding changes in the N-methyl-D-aspartate (NMDA) receptor complex in AD. We wished to elucidate the hypothesis that the NMDA receptor system is involved in the pathogenesis of AD using a gene expression approach targeting the mRNA of the universal subtype of the NMDA receptor NR1. This was performed using in situ hybridization and antisense 35S-labelled oligonucleotides on brain tissue collected at post-mortem. Relative mRNA expression was measured in standardised optical density units (OD units) using videodensitometry without knowledge of the diagnosis. The study population consisted of AD (n = 6) and neurodegenerative non-Alzheimer controls (non-AD, n = 14). Gene expression was measured in the frontal lobe, superior temporal gyrus and three areas within the hippocampus. We have observed no significant differences in the relative mRNA expression of the NR1 subtype of glutamate receptor in the following regions: frontal lobe AD = 60.7 +/- 14.1 OD units mRNA (x +/- 1SE) vs 52.6 +/- 1 in non-AD (Mann-Whitney test, p = 0.477); the superior temporal gyrus: AD = 53.3 +/- 13.9 vs 38.2 +/- 7 (p = 0.37); the CA1 region: AD = 37.8 +/- 7.75 vs 81.5 +/- 25.7 (p = 0.66); subiculum AD = 46.7 +/- 11.0 vs 105 +/- 43.3 (p = 0.82); parahippocampal gyrus AD = 36.6 +/- 9.3 vs 81.7 +/- 40.6 (p = 0.90). There were trends to a reduction in NR1 mRNA in the hippocampus and increased NR1 within the frontal and superficial temporal gyrus which were not significant. There was variation within and between all patients with and without AD in the magnitude of NR1 expression in all anatomical regions studied. The findings suggest heterogeneity in the involvement of the post-synaptic glutamatergic system in AD.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Brain

KW - Female

KW - Frontal Lobe

KW - Hippocampus

KW - Humans

KW - In Situ Hybridization

KW - Male

KW - Middle Aged

KW - Neurodegenerative Diseases

KW - RNA, Messenger

KW - Receptors, N-Methyl-D-Aspartate

KW - Temporal Lobe

KW - Comparative Study

KW - Journal Article

U2 - 10.1007/s007020200006

DO - 10.1007/s007020200006

M3 - Article

VL - 109

SP - 77

EP - 89

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

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ER -