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Article

Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors

Institute of Pathophysiology, Focus Program Translational Neuroscience (FTN), University Medical Center of the Johannes Gutenberg, University Mainz, 55128 Mainz, Germany
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Author to whom correspondence should be addressed.
Academic Editor: Arkadiusz Orzechowski
Int. J. Mol. Sci. 2021, 22(12), 6298; https://doi.org/10.3390/ijms22126298
Received: 4 May 2021 / Revised: 7 June 2021 / Accepted: 9 June 2021 / Published: 11 June 2021
(This article belongs to the Special Issue Pathogenesis of Alzheimer's Disease)
Onset and progression of Alzheimer’s 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 (Aβ) toxicity. NMDAR expression, on the other hand, can be affected by Aβ. We tested whether the high vulnerability of neocortical neurons for Aβ-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Aβ. 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 Aβ-toxicity. Spine number was decreased in pyramidal cells of 5xFAD mice and increased in neurons with 3-week virus-mediated Aβ-overexpression. NMDARs were required for both Aβ-mediated changes in spine number and functional synapses. Thus, our study gives novel insights into the Aβ-mediated regulation of NMDAR expression and the role of NMDARs in Aβ pathophysiology in the somatosensory cortex. View Full-Text
Keywords: Alzheimer’s disease; 5xFAD; Amyloid beta; NMDAR; somatosensory cortex Alzheimer’s disease; 5xFAD; Amyloid beta; NMDAR; somatosensory cortex
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MDPI and ACS Style

Back, M.K.; Ruggieri, S.; Jacobi, E.; von Engelhardt, J. Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors. Int. J. Mol. Sci. 2021, 22, 6298. https://doi.org/10.3390/ijms22126298

AMA Style

Back MK, Ruggieri S, Jacobi E, von Engelhardt J. Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors. International Journal of Molecular Sciences. 2021; 22(12):6298. https://doi.org/10.3390/ijms22126298

Chicago/Turabian Style

Back, Michaela K., Sonia Ruggieri, Eric Jacobi, and Jakob von Engelhardt. 2021. "Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors" International Journal of Molecular Sciences 22, no. 12: 6298. https://doi.org/10.3390/ijms22126298

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