Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission

Glutamic acid decarboxylase of 65 kDa (GAD65) antibodies have been reported in a variety of neurological disorders such as stiff-person syndrome (SPS), sporadic ataxia and some cases of epilepsy. Since the target is believed to be the cytoplasmic enzyme GAD65, the key enzyme of γ-aminobutyric acid (...

Full description

Bibliographic Details
Main Authors:	Hackert, Jana K., Müller, Lorenz, Rohde, Marco, Bien, Christian G., Köhling, Rüdiger, Kirschstein, Timo
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870265/

id	pubmed-4870265
recordtype	oai_dc
spelling	pubmed-48702652016-05-30 Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission Hackert, Jana K. Müller, Lorenz Rohde, Marco Bien, Christian G. Köhling, Rüdiger Kirschstein, Timo Neuroscience Glutamic acid decarboxylase of 65 kDa (GAD65) antibodies have been reported in a variety of neurological disorders such as stiff-person syndrome (SPS), sporadic ataxia and some cases of epilepsy. Since the target is believed to be the cytoplasmic enzyme GAD65, the key enzyme of γ-aminobutyric acid (GABA) synthesis, the pathophysiological role of these antibodies is poorly understood. Here, we stereotactically injected human cerebrospinal fluid (CSF) containing GAD65-antibodies into the hippocampus of rats in vivo and then prepared hippocampal slices 1–2 days after post-operative recovery. We characterized both evoked and spontaneous GABAergic transmission in vitro using sharp microelectrode and patch-clamp recordings in CA1 neurons. Intracellular recordings with sharp microelectrodes from CA1 neurons showed that evoked GABAAR- or GABABR-mediated inhibitory postsynaptic potentials (IPSP) remained unaltered in anti-GAD65 tissue. These results were confirmed with patch-clamp recordings showing no difference in evoked gabazine-sensitive inhibitory postsynaptic currents (IPSCs). In addition, spontaneous IPSCs also showed no difference between anti-GAD65 tissue and controls with respect to the mean frequency, the mean amplitude and the sIPSC distribution. In conclusion, stereotactic injection of GAD65-antibodies into the hippocampus leaves evoked and spontaneous GABAergic synaptic transmission intact. Hence, dysfunction of the inhibitory GABAergic system does not appear to be the major mechanism of epileptogenicity in this disease. Frontiers Media S.A. 2016-05-18 /pmc/articles/PMC4870265/ /pubmed/27242441 http://dx.doi.org/10.3389/fncel.2016.00130 Text en Copyright © 2016 Hackert, Müller, Rohde, Bien, Köhling and Kirschstein. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hackert, Jana K. Müller, Lorenz Rohde, Marco Bien, Christian G. Köhling, Rüdiger Kirschstein, Timo
spellingShingle	Hackert, Jana K. Müller, Lorenz Rohde, Marco Bien, Christian G. Köhling, Rüdiger Kirschstein, Timo Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
author_facet	Hackert, Jana K. Müller, Lorenz Rohde, Marco Bien, Christian G. Köhling, Rüdiger Kirschstein, Timo
author_sort	Hackert, Jana K.
title	Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
title_short	Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
title_full	Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
title_fullStr	Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
title_full_unstemmed	Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission
title_sort	anti-gad65 containing cerebrospinal fluid does not alter gabaergic transmission
description	Glutamic acid decarboxylase of 65 kDa (GAD65) antibodies have been reported in a variety of neurological disorders such as stiff-person syndrome (SPS), sporadic ataxia and some cases of epilepsy. Since the target is believed to be the cytoplasmic enzyme GAD65, the key enzyme of γ-aminobutyric acid (GABA) synthesis, the pathophysiological role of these antibodies is poorly understood. Here, we stereotactically injected human cerebrospinal fluid (CSF) containing GAD65-antibodies into the hippocampus of rats in vivo and then prepared hippocampal slices 1–2 days after post-operative recovery. We characterized both evoked and spontaneous GABAergic transmission in vitro using sharp microelectrode and patch-clamp recordings in CA1 neurons. Intracellular recordings with sharp microelectrodes from CA1 neurons showed that evoked GABAAR- or GABABR-mediated inhibitory postsynaptic potentials (IPSP) remained unaltered in anti-GAD65 tissue. These results were confirmed with patch-clamp recordings showing no difference in evoked gabazine-sensitive inhibitory postsynaptic currents (IPSCs). In addition, spontaneous IPSCs also showed no difference between anti-GAD65 tissue and controls with respect to the mean frequency, the mean amplitude and the sIPSC distribution. In conclusion, stereotactic injection of GAD65-antibodies into the hippocampus leaves evoked and spontaneous GABAergic synaptic transmission intact. Hence, dysfunction of the inhibitory GABAergic system does not appear to be the major mechanism of epileptogenicity in this disease.
publisher	Frontiers Media S.A.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870265/
_version_	1613580460114313216

Anti-GAD65 Containing Cerebrospinal Fluid Does not Alter GABAergic Transmission

Similar Items