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

Research output: Contribution to journalArticlepeer-review

163 Scopus citations

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.

Original languageEnglish
Pages (from-to)156-161
Number of pages6
JournalBrain Research
Volume399
Issue number1
DOIs
StatePublished - Dec 3 1986

Bibliographical 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.

Keywords

  • Alzheimer's disease
  • Excitatory amino acid receptor
  • Glutamate
  • Hippocampus
  • N-methyl-d-aspartate
  • NMDA

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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