Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease

James W. Geddes; Helena Chang-Chui; Suzanne M. Cooper; Ira T. Lott; Carl W. Cotman

doi:10.1016/0006-8993(86)90611-6

Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease

James W. Geddes
, Helena Chang-Chui
, Suzanne M. Cooper
, Ira T. Lott
, Carl W. Cotman

Neuroscience

Producción científica: Article › revisión exhaustiva

164 Citas (Scopus)

Resumen

We examined the distribution and density of N-methyl-d-aspartate (NMDA) displaceable l-[³H] glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.

Idioma original	English
Páginas (desde-hasta)	156-161
Número de páginas	6
Publicación	Brain Research
Volumen	399
N.º	1
DOI	https://doi.org/10.1016/0006-8993(86)90611-6
Estado	Published - dic 3 1986

Nota bibliográfica

Funding Information:
mage3° , as do excitotoxinasc tinga t NMDA receptors2 s. MoreoverN, MDA receptoar ntagonistesf fec-tivelyp reventth es econdarnye uronadl amagere sult-ing from epilepsyi,s chemiaa ndh ypoglycem1i7a,t s,29. The recentr eportt hat glutamatea nd aspartatein - ducep airedh elicalf ilamenfto rmationin culturedh u-mann euronsim pliest hate xcitatoraym inoa cidsm ay be involvedin thep athophysioloogfy A D 6. In animalm odelst, hev ulnerabilitoyf corticaal nd subcorticarle gionst o excitotoxiicn sultsa ppearsto correlatew ith NMDA receptodr ensit2yt ,32T. he cor-respondencbee tweenN MDA receptodr ensitya nd the predilectionfo r AD-neuropathologiny the human hippocampuiss consistenwt ith a possiblei n-volvemenot f excitotoximc echanismins the patho-genesios f this diseaseN. MDA receptorasr econcen-tratedin CAt, subiculuma, ndin the outerl ayerso f thee ntorhinaclo rtexa, ll of whichc onsistenthlya vea high numbero f tangles,g ranulovaculadre generation, and Hirano bodiesi n AD 2. Furthermoret,h e dentateg yrusm oleculalra yer,also rich in NMDA receptorsh,a sa predilectiofno r neuriticp laque1s5 .I f excitotoximc echanismdso contributeto the patho-physiologoyf Alzheimer'ds iseaseN, MDA receptor antagonisrtes presenpto tentiatlh erapeutaicg ents: We thankR .C. Kim, B. Choi, U.T. Slagera ndC. Miller for clinical and neuropathologiceavla luation and D.T. Monaghanfo r technicaal dvicea nd con-structivec ommentrse gardingth e manuscriptT. his work was supportedb y NIA Grant P50AG5142. J.W.G. is the recipiento f a National Down SyndromeS ocietyS cienceS cholarA ward.

Financiación

mage3° , as do excitotoxinasc tinga t NMDA receptors2 s. MoreoverN, MDA receptoar ntagonistesf fec-tivelyp reventth es econdarnye uronadl amagere sult-ing from epilepsyi,s chemiaa ndh ypoglycem1i7a,t s,29. The recentr eportt hat glutamatea nd aspartatein - ducep airedh elicalf ilamenfto rmationin culturedh u-mann euronsim pliest hate xcitatoraym inoa cidsm ay be involvedin thep athophysioloogfy A D 6. In animalm odelst, hev ulnerabilitoyf corticaal nd subcorticarle gionst o excitotoxiicn sultsa ppearsto correlatew ith NMDA receptodr ensit2yt ,32T. he cor-respondencbee tweenN MDA receptodr ensitya nd the predilectionfo r AD-neuropathologiny the human hippocampuiss consistenwt ith a possiblei n-volvemenot f excitotoximc echanismins the patho-genesios f this diseaseN. MDA receptorasr econcen-tratedin CAt, subiculuma, ndin the outerl ayerso f thee ntorhinaclo rtexa, ll of whichc onsistenthlya vea high numbero f tangles,g ranulovaculadre generation, and Hirano bodiesi n AD 2. Furthermoret,h e dentateg yrusm oleculalra yer,also rich in NMDA receptorsh,a sa predilectiofno r neuriticp laque1s5 .I f excitotoximc echanismdso contributeto the patho-physiologoyf Alzheimer'ds iseaseN, MDA receptor antagonisrtes presenpto tentiatlh erapeutaicg ents: We thankR .C. Kim, B. Choi, U.T. Slagera ndC. Miller for clinical and neuropathologiceavla luation and D.T. Monaghanfo r technicaal dvicea nd con-structivec ommentrse gardingth e manuscriptT. his work was supportedb y NIA Grant P50AG5142. J.W.G. is the recipiento f a National Down SyndromeS ocietyS cienceS cholarA ward.

Financiadores	Número del financiador
National Institute on Aging	P50AG005142

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/0006-8993(86)90611-6

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@article{643820d8a883471b9c975c2216350b93,

title = "Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease",

abstract = "We examined the distribution and density of N-methyl-d-aspartate (NMDA) displaceable l-[3H] glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.",

keywords = "Alzheimer's disease, Excitatory amino acid receptor, Glutamate, Hippocampus, N-methyl-d-aspartate, NMDA",

author = "Geddes, \{James W.\} and Helena Chang-Chui and Cooper, \{Suzanne M.\} and Lott, \{Ira T.\} and Cotman, \{Carl W.\}",

note = "Funding Information: mage3° , as do excitotoxinasc tinga t NMDA receptors2 s. MoreoverN, MDA receptoar ntagonistesf fec-tivelyp reventth es econdarnye uronadl amagere sult-ing from epilepsyi,s chemiaa ndh ypoglycem1i7a,t s,29. The recentr eportt hat glutamatea nd aspartatein - ducep airedh elicalf ilamenfto rmationin culturedh u-mann euronsim pliest hate xcitatoraym inoa cidsm ay be involvedin thep athophysioloogfy A D 6. In animalm odelst, hev ulnerabilitoyf corticaal nd subcorticarle gionst o excitotoxiicn sultsa ppearsto correlatew ith NMDA receptodr ensit2yt ,32T. he cor-respondencbee tweenN MDA receptodr ensitya nd the predilectionfo r AD-neuropathologiny the human hippocampuiss consistenwt ith a possiblei n-volvemenot f excitotoximc echanismins the patho-genesios f this diseaseN. MDA receptorasr econcen-tratedin CAt, subiculuma, ndin the outerl ayerso f thee ntorhinaclo rtexa, ll of whichc onsistenthlya vea high numbero f tangles,g ranulovaculadre generation, and Hirano bodiesi n AD 2. Furthermoret,h e dentateg yrusm oleculalra yer,also rich in NMDA receptorsh,a sa predilectiofno r neuriticp laque1s5 .I f excitotoximc echanismdso contributeto the patho-physiologoyf Alzheimer'ds iseaseN, MDA receptor antagonisrtes presenpto tentiatlh erapeutaicg ents: We thankR .C. Kim, B. Choi, U.T. Slagera ndC. Miller for clinical and neuropathologiceavla luation and D.T. Monaghanfo r technicaal dvicea nd con-structivec ommentrse gardingth e manuscriptT. his work was supportedb y NIA Grant P50AG5142. J.W.G. is the recipiento f a National Down SyndromeS ocietyS cienceS cholarA ward.",

year = "1986",

month = dec,

day = "3",

doi = "10.1016/0006-8993(86)90611-6",

language = "English",

volume = "399",

pages = "156--161",

number = "1",

}

TY - JOUR

T1 - Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease

AU - Geddes, James W.

AU - Chang-Chui, Helena

AU - Cooper, Suzanne M.

AU - Lott, Ira T.

AU - Cotman, Carl W.

N1 - Funding Information: mage3° , as do excitotoxinasc tinga t NMDA receptors2 s. MoreoverN, MDA receptoar ntagonistesf fec-tivelyp reventth es econdarnye uronadl amagere sult-ing from epilepsyi,s chemiaa ndh ypoglycem1i7a,t s,29. The recentr eportt hat glutamatea nd aspartatein - ducep airedh elicalf ilamenfto rmationin culturedh u-mann euronsim pliest hate xcitatoraym inoa cidsm ay be involvedin thep athophysioloogfy A D 6. In animalm odelst, hev ulnerabilitoyf corticaal nd subcorticarle gionst o excitotoxiicn sultsa ppearsto correlatew ith NMDA receptodr ensit2yt ,32T. he cor-respondencbee tweenN MDA receptodr ensitya nd the predilectionfo r AD-neuropathologiny the human hippocampuiss consistenwt ith a possiblei n-volvemenot f excitotoximc echanismins the patho-genesios f this diseaseN. MDA receptorasr econcen-tratedin CAt, subiculuma, ndin the outerl ayerso f thee ntorhinaclo rtexa, ll of whichc onsistenthlya vea high numbero f tangles,g ranulovaculadre generation, and Hirano bodiesi n AD 2. Furthermoret,h e dentateg yrusm oleculalra yer,also rich in NMDA receptorsh,a sa predilectiofno r neuriticp laque1s5 .I f excitotoximc echanismdso contributeto the patho-physiologoyf Alzheimer'ds iseaseN, MDA receptor antagonisrtes presenpto tentiatlh erapeutaicg ents: We thankR .C. Kim, B. Choi, U.T. Slagera ndC. Miller for clinical and neuropathologiceavla luation and D.T. Monaghanfo r technicaal dvicea nd con-structivec ommentrse gardingth e manuscriptT. his work was supportedb y NIA Grant P50AG5142. J.W.G. is the recipiento f a National Down SyndromeS ocietyS cienceS cholarA ward.

PY - 1986/12/3

Y1 - 1986/12/3

N2 - We examined the distribution and density of N-methyl-d-aspartate (NMDA) displaceable l-[3H] glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.

AB - We examined the distribution and density of N-methyl-d-aspartate (NMDA) displaceable l-[3H] glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields.

KW - Alzheimer's disease

KW - Excitatory amino acid receptor

KW - Glutamate

KW - Hippocampus

KW - N-methyl-d-aspartate

KW - NMDA

UR - https://www.scopus.com/pages/publications/0023000880

UR - https://www.scopus.com/pages/publications/0023000880#tab=citedBy

U2 - 10.1016/0006-8993(86)90611-6

DO - 10.1016/0006-8993(86)90611-6

M3 - Article

C2 - 2879613

AN - SCOPUS:0023000880

SN - 0006-8993

VL - 399

SP - 156

EP - 161

JO - Brain Research

JF - Brain Research

IS - 1

ER -

Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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