@Article{dbt_mods_00059693,
  author = 	{Ceanga, Mihai
		and Rahmati, Vahid
		and Haselmann, Holger
		and Schmidl, Lars
		and Hunter, Daniel
		and Brauer, Anna-Katherina
		and Liebscher, Sabine
		and Kreye, Jakob
		and Pr{\"u}ss, Harald
		and Groc, Laurent
		and Hallermann, Stefan
		and Dalmau, Josep
		and Ori, Alessandro
		and Heckmann, Manfred
		and Geis, Christian},
  title = 	{Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony},
  journal = 	{Cell reports},
  year = 	{2023},
  month = 	{Oct},
  day = 	{31},
  publisher = 	{Cell Press},
  address = 	{Maryland Heights, MO},
  volume = 	{42},
  number = 	{10},
  abstract = 	{Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal uid or human monoclonal anti-GluN1- autoantibodies in mice, we nd a disrupted excitatory- inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission. NMDAR-Abs amplify network g oscillations and disrupt q-g coupling. A data-informed network model reveals that lower AMPAR strength and faster GABAA receptor current kinetics chiey account for these abnormal oscillations. As predicted in silico and evidenced ex vivo, positive allosteric modulation of AMPARs alleviates aberrant g activity, reinforcing the causative effects of the excitatory-inhibitory imbalance. Collectively, NMDAR-Ab-induced aberrant synaptic, cellular, and network dynamics provide conceptual insights into NMDAR-Ab-mediated pathomechanisms and reveal promising therapeutic targets that merit future in vivo validation.},
  note = 	{Zweitver{\"o}ffentlichung},
  note = 	{Volume 1, issue 1 (22 January 2020)-},
  note = 	{Unterreihe: Physical science},
  issn = 	{2666-3864},
  doi = 	{10.1016/j.celrep.2023.113166},
  url = 	{https://www.db-thueringen.de/receive/dbt_mods_00059693},
  url = 	{http://uri.gbv.de/document/gvk:ppn:1694210766},
  url = 	{https://doi.org/10.1016/j.celrep.2023.113166},
  file = 	{:https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00062380/1-s2.0-S2211124723011786-main.pdf:PDF},
  language = 	{en}
}