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Interactions of Human Autoantibodies with Hippocampal GABAergic Synaptic Transmission – Analyzing Antibody-Induced Effects ex vivo

Overview of attention for article published in Frontiers in Neurology, June 2015
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Title
Interactions of Human Autoantibodies with Hippocampal GABAergic Synaptic Transmission – Analyzing Antibody-Induced Effects ex vivo
Published in
Frontiers in Neurology, June 2015
DOI 10.3389/fneur.2015.00136
Pubmed ID
Authors

Holger Haselmann, Luise Röpke, Christian Werner, Albrecht Kunze, Christian Geis

Abstract

Autoantibodies (aAB) to the presynaptic located enzyme glutamate decarboxylase 65 (GAD65) are a characteristic attribute for a variety of autoimmune diseases of the central nervous system including subtypes of limbic encephalitis, stiff person-syndrome, cerebellar ataxia, and Batten's disease. Clinical signs of hyperexcitability and improvement of disease symptoms upon immunotherapy in some of these disorders suggest a possible pathogenic role of associated aAB. Recent experimental studies report inconsistent results regarding a direct pathogenic influence of anti-GAD65 aAB affecting inhibitory synaptic transmission in central GABAergic pathways. We here provide a method for direct evaluation of aAB-induced pathomechanisms in the intact hippocampal network. Purified patient IgG fractions containing aAB to GAD65 together with fixable lipophilic styryl dyes (FMdyes) are stereotactically injected into the hilus and the dentate gyrus in anesthetized mice. Twenty-four hours after intrahippocampal injection, acute hippocampal slices are prepared and transferred to a patch-clamp recording setup equipped with a fluorescence light source. Intraneural incorporated FMdyes show correct injection site for patch-clamp recording. Whole-cell patch-clamp recordings are performed from granule cells in the dentate gyrus and extracellular stimulation is applied in the border area of the dentate gyrus-hilus region to stimulate GABAergic afferents arising from parvalbumin positive basket cells. GABA-A receptor mediated inhibitory postsynaptic currents (IPSC) and miniature IPSC are recorded after blocking glutamatergic transmission. This approach allows investigation of potential aAB-induced effects on GABA-A receptor signaling ex vivo in an intact neuronal network. This offers several advantages compared to experimental procedures used in previous studies by in vitro AB preincubation of primary neurons or slice preparations. Furthermore, this method requires only small amounts of patient material that are often limited in rare diseases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 19%
Researcher 4 15%
Other 3 12%
Student > Doctoral Student 2 8%
Student > Postgraduate 2 8%
Other 5 19%
Unknown 5 19%
Readers by discipline Count As %
Medicine and Dentistry 9 35%
Neuroscience 6 23%
Sports and Recreations 1 4%
Unspecified 1 4%
Physics and Astronomy 1 4%
Other 0 0%
Unknown 8 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 July 2015.
All research outputs
#14,226,014
of 22,807,037 outputs
Outputs from Frontiers in Neurology
#5,744
of 11,670 outputs
Outputs of similar age
#138,253
of 266,832 outputs
Outputs of similar age from Frontiers in Neurology
#47
of 76 outputs
Altmetric has tracked 22,807,037 research outputs across all sources so far. This one is in the 35th percentile – i.e., 35% of other outputs scored the same or lower than it.
So far Altmetric has tracked 11,670 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.4. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
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