title: Altered postnatal maturation of striatal GABAergic interneurons in a phenotypic animal model of dystonia.
abstract: GABAergic disinhibition has been suggested to play a critical role in the pathophysiology of several basal ganglia disorders, including dystonia, a common movement disorder. Previous studies have shown a deficit of striatal GABAergic interneurons (IN) in the dtszmutant hamster, one of the few phenotypic animal models of dystonia. However, mechanisms underlying this deficit are largely unknown. In the present study, we investigated the migration and maturation of striatal IN during postnatal development (18days of age) and at age of highest severity of dystonia (33days of age) in this hamster model. In line with previous findings, the density of GAD67-positive IN and the level of parvalbumin mRNA, a marker for fast spiking GABAergic IN, were lower in the dtszmutant than in control hamsters. However, an unaltered density of Nkx2.1 labeled cells and Nkx2.1 mRNA level suggested that the migration of GABAergic IN into the striatum was not retarded. Therefore, different factors that indicate maturation of GABAergic IN were determined. While mRNA of the KCC2 cation/chloride transporters and the cytosolic carboanhydrase VII, used as markers for the so called GABA switch, as well as BDNF were unaltered, we found a reduced number of IN expressing the alpha1 subunit of the GABAA-receptor (37.5%) in dtszhamsters at an age of 33days, but not after spontaneous remission of dystonia at an age of 90days. Since IN shift expression from alpha2 to alpha1 subunits during postnatal maturation, this result together with a decreased parvalbumin mRNA expression suggest a delayed maturation of striatal GABAergic IN in this animal model, which might underlie abnormal neuronal activity and striatal plasticity.
authors: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors: Christoph
authors: C
authors: Bode
authors: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany. Electronic address: franziska.richter@vmf.uni-leipzig.de.
authors: Franziska
authors: F
authors: Richter
authors: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors: Christine
authors: C
authors: Spröte
authors: Institute for Physiology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany; Center of Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany.
authors: Tanja
authors: T
authors: Brigadski
authors: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors: Anne
authors: A
authors: Bauer
authors: Institute of Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany.
authors: Simone
authors: S
authors: Fietz
authors: Institute of Pharmacology and Toxicology, University of Zurich, Zurich 8057, Switzerland.
authors: Jean-Marc
authors: JM
authors: Fritschy
authors: Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany. Electronic address: angelika.richter@vetmed.uni-leipzig.de.
authors: Angelika
authors: A
authors: Richter
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000254:growth & development* / Q000473:pathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D004421:Dystonia / Q000235:genetics / Q000473:pathology*; D005260:Female; D059330:GABAergic Neurons / Q000201:enzymology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008647:Mesocricetus / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D019204:GTP-Binding Proteins; D005968:Glutamate Decarboxylase; D009687:Nuclear Proteins; D010320:Parvalbumins; D011963:Receptors, GABA-A; D027981:Symporters; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D000096922:K Cl- Cotransporters; C402565:glutamate decarboxylase 1
keywords: BDNF; Basal ganglia; Dyskinesia; Fast spiking interneurons; GABA; Parvalbumin; Striatum