Defective synaptic transmission causes disease signs in a mouse model of Juvenile Neuronal Ceroid Lipofuscinosis

Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system 
Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3Δex1-6) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition.
show moreshow less

Metadaten
Author:Benedikt Grünewald, Maren Denise Lange, Christian Werner, Aet O'Leary, Andreas Weishaupt, Sandy Popp, David A. Pearce, Heinz Wiendl, Andreas Reif, Hans-Christoph Pape, Klaus Viktor Toyka, Claudia Sommer, Christian Geis
URN:urn:nbn:de:hebis:30:3-450592
DOI:http://dx.doi.org/10.7554/eLife.28685
ISSN:2050-084X
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29135436
Parent Title (English):eLife
Publisher:eLife Sciences Publications
Place of publication:Cambridge
Contributor(s):Christian Rosenmund
Document Type:Article
Language:English
Year of Completion:2017
Date of first Publication:2017/11/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/12/05
Tag:Amygdala; Batten disease; Cln3; Gaba; Hippocampus; Neuroscience; Research article; Synaptic dysfunction
Volume:6
Issue:e28685
Pagenumber:28
First Page:1
Last Page:28
Note:
Copyright Grünewald et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
HeBIS PPN:424952165
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

$Rev: 11761 $