PMID- 30108497
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-3563 (Print)
IS  - 1663-3563 (Electronic)
IS  - 1663-3563 (Linking)
VI  - 10
DP  - 2018
TI  - Differentially Altered NMDAR Dependent and Independent Long-Term Potentiation in 
      the CA3 Subfield in a Model of Anti-NMDAR Encephalitis.
PG  - 26
LID - 10.3389/fnsyn.2018.00026 [doi]
LID - 26
AB  - Purpose: Autoantibodies against NMDA receptors (NMDAR) in the cerebrospinal fluid 
      (CSF) from anti-NMDAR encephalitis patients have been suggested to be pathogenic 
      since in previous studies using patient CSF, NMDAR-dependent processes such as 
      long-term potentiation (LTP) were compromised. However, autoantibodies may 
      represent a family of antibodies targeted against different epitopes, and CSF may 
      contain further autoantibodies. Here, we tested the specificity of the 
      autoantibody by comparing NMDAR-dependent and NMDAR-independent LTP within the 
      same hippocampal subfield, CA3, using CSF samples from four anti-NMDAR 
      encephalitis patients and three control patients. Methods: We performed a 
      stereotactic injection of patient-derived cell-free CSF with proven presence or 
      absence of NMDAR-antibodies into the rat hippocampus in vivo. Hippocampal brain 
      slices were prepared 1-8 days after intrahippocampal injection, and 
      NMDAR-dependent LTP at the associational-commissural (A/C) fiber-CA3 synapse was 
      compared to NMDAR-independent LTP at the mossy fiber (MF)-CA3 synapse. Results: 
      The LTP magnitude at A/C fiber-CA3 synapses in slices from control-CSF-treated 
      animals (168 +/- 8% n = 54) was significantly higher than LTP in slices from 
      NMDAR-CSF-treated animals (139 +/- 9%, n = 40; P = 0.015), although there was some 
      variation between the individual CSF samples. We found residual LTP in 
      NMDAR-CSF-treated tissue which could be abolished by the NMDAR inhibitor D-AP5. 
      Moreover, the CA3 field excitatory postsynaptic potential (fEPSP) was followed by 
      epileptiform afterpotentials in 5% of slices (4/78) from control-CSF-treated 
      animals, but in 26% of slices (12/46) from NMDAR-CSF-treated animals (P = 0.002). 
      Application of the LTP-inducing paradigm increased the proportion of slices with 
      epileptiform afterpotentials, but D-AP5 significantly reduced the occurrence of 
      epileptiform afterpotentials only in NMDAR-CSF-treated, but not in control 
      tissue. At the MF synapse, no significant difference in LTP values of control-CSF 
      and in NMDAR-CSF-treated tissue was observed indicating that NMDAR-independent 
      MF-LTP is intact in NMDAR-CSF-treated tissue. Conclusion: These findings indicate 
      that anti-NMDAR containing CSF impairs LTP at the A/C fiber-CA3 synapse, although 
      there is substantial variation among CSF samples suggesting different epitopes 
      among patient-derived antibodies. The differential inhibition of LTP at this 
      synapse in contrast to the MF-CA3 synapse suggests the specificity and underlines 
      the pathophysiological role of the NMDAR-antibody.
FAU - Blome, Roman
AU  - Blome R
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Bach, Willi
AU  - Bach W
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Guli, Xiati
AU  - Guli X
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Porath, Katrin
AU  - Porath K
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Sellmann, Tina
AU  - Sellmann T
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Bien, Christian G
AU  - Bien CG
AD  - Epilepsy Center Bethel, Krankenhaus Mara, Bielefeld, Germany.
FAU - Kohling, Rudiger
AU  - Kohling R
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
FAU - Kirschstein, Timo
AU  - Kirschstein T
AD  - Oscar Langendorff Institute of Physiology, University of Rostock, Rostock, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20180731
PL  - Switzerland
TA  - Front Synaptic Neurosci
JT  - Frontiers in synaptic neuroscience
JID - 101548972
PMC - PMC6079239
OTO - NOTNLM
OT  - LTP
OT  - NMDA receptor
OT  - associational-commissural fibers
OT  - epileptiform afterpotentials
OT  - mossy fibers
EDAT- 2018/08/16 06:00
MHDA- 2018/08/16 06:01
PMCR- 2018/01/01
CRDT- 2018/08/16 06:00
PHST- 2018/03/30 00:00 [received]
PHST- 2018/07/11 00:00 [accepted]
PHST- 2018/08/16 06:00 [entrez]
PHST- 2018/08/16 06:00 [pubmed]
PHST- 2018/08/16 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnsyn.2018.00026 [doi]
PST - epublish
SO  - Front Synaptic Neurosci. 2018 Jul 31;10:26. doi: 10.3389/fnsyn.2018.00026. 
      eCollection 2018.