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Distinct Effects of Stereotactically Injected Human Cerebrospinal Fluid Containing Glutamic Acid Decarboxylase Antibodies into the Hippocampus of Rats on the Development of Spontaneous Epileptic Activity

1
Oscar Langendorff Institute of Physiology, University of Rostock, 18057 Rostock, Germany
2
Department of Irradiation Therapy, University Hospital of Rostock, 18059 Rostock, Germany
3
Epilepsy Center Bethel, Krankenhaus Mara, 33617 Bielefeld, Germany
4
Center of Transdisciplinary Neurosciences Rostock, University of Rostock, 18147 Rostock, Germany
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(2), 123; https://doi.org/10.3390/brainsci10020123
Received: 9 February 2020 / Revised: 17 February 2020 / Accepted: 20 February 2020 / Published: 22 February 2020
(This article belongs to the Special Issue Synaptic Changes in Epilepsy)
Background: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that anti-GAD autoantibodies could diminish the GABA content in the slice and facilitate epileptic activity. Methods: Cerebrospinal fluids (CSF) from two patients containing anti-GAD (A and B) were injected into the rat hippocampus in vivo. Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg2+ and/or by adding gabazine. As control groups, we injected an anti-GAD-negative human CSF or saline solution, and we used non-operated naive animals. Results: RED frequencies were significantly higher in the Mg2+-free solution than in the gabazine-containing solution. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg2+-free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. Conclusions: These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity. View Full-Text
Keywords: glutamic acid decarboxylase; autoimmune limbic encephalitis; NMDA and GABA receptor; recurrent epileptiform discharges; human cerebrospinal fluid; hippocampus of rats; field potential recording glutamic acid decarboxylase; autoimmune limbic encephalitis; NMDA and GABA receptor; recurrent epileptiform discharges; human cerebrospinal fluid; hippocampus of rats; field potential recording
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Frerker, B.; Rohde, M.; Müller, S.; Bien, C.G.; Köhling, R.; Kirschstein, T. Distinct Effects of Stereotactically Injected Human Cerebrospinal Fluid Containing Glutamic Acid Decarboxylase Antibodies into the Hippocampus of Rats on the Development of Spontaneous Epileptic Activity. Brain Sci. 2020, 10, 123.

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