{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:03:16Z","timestamp":1790359396683,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T00:00:00Z","timestamp":1247788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[2009,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Greater than 90% of familial Alzheimer's disease (AD) is linked to mutations of presenilin (PS), and the loss of PS function altogether within mouse brains by conditional double knockout of the PS 1 and 2 genes (PS\u2010cDKO) leads to age\u2010dependent emergence of AD phenotypes, including neurodegeneration and reduced synaptic plasticity in the hippocampal CA1. The goal of our study was to identify the ultrastructural and molecular changes at synapses in the hippocampal CA1 of this PS\u2010cDKO mouse model of AD. We examined the asymmetric (excitatory) synapses formed on apical dendrites of CA1 pyramidal neurons at 2 months postnatal, an age when AD\u2010like symptoms emerge but brain morphology, as assessed by light microscopy, is still normal. Our quantitative electron microscopic analyses confirm that PS\u2010cDKO hippocampi at 2 months postnatal do not yet exhibit synapse losses or spine size alterations. However, immunocytochemistry reveals that the same region exhibits a 28% increase in the proportion of spines labeled for the NR2A subunits of NMDA receptors (NMDAR), with a 31% increase specifically at postsynaptic densities and a concomitant reduction of these subunits at nonsynaptic sites within spine heads. In contrast, no change in levels or the distribution pattern of NR2B subunit levels were detected within spine heads. Presynaptically, NR2A levels are elevated at axo\u2010spinous junctions and these may contribute to the timing\u2010dependent, long\u2010term depression. These observations point to an early\u2010onset trapping of NMDAR at synapses that are subtle but may underlie the reduced synaptic plasticity at 2 months of age and excitotoxicity at later stages. J. Comp. Neurol. 517:512\u2013523, 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.22151","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T20:45:06Z","timestamp":1247863506000},"page":"512-523","source":"Crossref","is-referenced-by-count":13,"title":["Increased levels of NMDA receptor NR2A subunits at pre\u2010 and postsynaptic sites of the hippocampal CA1: An early response to conditional double knockout of presenilin 1 and 2"],"prefix":"10.1002","volume":"517","author":[{"given":"Chiye","family":"Aoki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermina","family":"Nedelescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tunazzina","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,9,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141215898"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20148"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-09-05202.1994"},{"key":"e_1_2_5_5_1","first-page":"535","article-title":"Use 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