Stereotactic injection of cerebrospinal fluid from anti-NMDA receptor encephalitis into rat dentate gyrus impairs NMDA receptor function

Till Würdemann, Maxi Kersten, Tursonjan Tokay, Xiati Guli, Maria Kober, Marco Rohde, Katrin Porath, Tina Sellmann, Christian G. Bien, Rüdiger Köhling, Timo Kirschstein

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Autoimmune encephalitis is increasingly recognized in patients with otherwise unexplained encephalopathy with epilepsy. Among these, patients with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis present epileptic seizures, memory deficits, and psychiatric symptoms. However, the functional consequences of such autoantibodies are poorly understood. In order to investigate the pathophysiology of this disease, we stereotactically injected either cerebrospinal fluid (CSF) from three anti-NMDAR encephalitis patients or commercially available anti-NMDAR1 into the dentate gyrus of adult female rats. Control animals were injected with either CSF obtained from three epilepsy patients (ganglioglioma, posttraumatic epilepsy, focal cortical dysplasia) lacking anti-NMDAR or saline. Intracellular recordings from dentate gyrus granule cells showed a significant reduction of the NMDAR-evoked excitatory postsynaptic potentials (NMDAR-EPSPs) in animals treated with anti-NMDAR. As a consequence of this, action potential firing in these cells by NMDAR-EPSPs was significantly impaired. Long-term potentiation in the dentate gyrus was also significantly reduced in rats injected with anti-NMDAR as compared to control animals. This was accompanied by a significantly impaired learning performance in the Morris water maze hidden platform task when the animals had been injected with anti-NMDAR antibody-containing CSF. Our findings suggest that anti-NMDAR lead to reduced NMDAR function in vivo which could contribute to the memory impairment found in patients with anti-NMDAR encephalitis.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalBrain Research
Volume1633
DOIs
Publication statusPublished - Feb 15 2016

Keywords

  • AMPA receptor
  • CNQX
  • GABA receptor
  • LTP
  • NR1
  • SR95531

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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  • Cite this

    Würdemann, T., Kersten, M., Tokay, T., Guli, X., Kober, M., Rohde, M., Porath, K., Sellmann, T., Bien, C. G., Köhling, R., & Kirschstein, T. (2016). Stereotactic injection of cerebrospinal fluid from anti-NMDA receptor encephalitis into rat dentate gyrus impairs NMDA receptor function. Brain Research, 1633, 10-18. https://doi.org/10.1016/j.brainres.2015.12.027