{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:44:12Z","timestamp":1788385452482,"version":"build-2803163510"},"reference-count":108,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003390","name":"Fritz Thyssen Stiftung","doi-asserted-by":"publisher","award":["AZ 10.15.1.017MN"],"award-info":[{"award-number":["AZ 10.15.1.017MN"]}],"id":[{"id":"10.13039\/501100003390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Onset and progression of Alzheimer\u2019s disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (A\u03b2) toxicity. NMDAR expression, on the other hand, can be affected by A\u03b2. We tested whether the high vulnerability of neocortical neurons for A\u03b2-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by A\u03b2. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1\/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD mice, extrasynaptic NMDARs seem to contain GluN1\/GluN2A and GluN1\/GluN2A\/GluN2B. We used conditional GluN1 and GluN2B knockout mice to investigate whether NMDARs contribute to A\u03b2-toxicity. Spine number was decreased in pyramidal cells of 5xFAD mice and increased in neurons with 3-week virus-mediated A\u03b2-overexpression. NMDARs were required for both A\u03b2-mediated changes in spine number and functional synapses. Thus, our study gives novel insights into the A\u03b2-mediated regulation of NMDAR expression and the role of NMDARs in A\u03b2 pathophysiology in the somatosensory cortex.<\/jats:p>","DOI":"10.3390\/ijms22126298","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T12:44:37Z","timestamp":1623415477000},"page":"6298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors"],"prefix":"10.3390","volume":"22","author":[{"given":"Michaela K.","family":"Back","sequence":"first","affiliation":[{"name":"Institute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg, University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg, University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Jacobi","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg, University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-3294","authenticated-orcid":false,"given":"Jakob","family":"von Engelhardt","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg, University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1001\/jama.283.12.1571","article-title":"Correlation Between Elevated Levels of Amyloid \u03b2-Peptide in the Brain and Cognitive Decline","volume":"283","author":"Haroutunian","year":"2000","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1212\/WNL.58.12.1791","article-title":"Phases of A\u03b2-deposition in the human brain and its relevance for the development of AD","volume":"58","author":"Thal","year":"2002","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1002\/cne.24555","article-title":"Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer\u2019s disease","volume":"527","author":"Whitesell","year":"2019","journal-title":"J. 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