title: Dysregulation of select ATP-dependent chromatin remodeling factors in high trait anxiety.
abstract: Enhanced anxiety is a salient feature of a number of psychiatric disorders including anxiety disorders, trauma-related disorders and depression. Although aberrant expression of various genes has been detected in patients suffering from persistent high anxiety as well as in high anxiety rodent models, the molecular mechanisms responsible for altered transcription regulation have been poorly addressed. Transcription regulation intimately involves the contribution of chromatin modifying processes, such as histone modification and ATP-dependent chromatin remodeling, yet their role in pathological anxiety is not known. Here, we investigated for the first time if altered levels of several ATP-dependent chromatin remodeling factors (ChRFs) and histone deacetylases (HDACs) may be linked to high trait anxiety in mice. While we found protein levels of the ChRFs SNF2H, ATRX, CHD1, CHD3 and CHD5 and of HDACs 1-3 and 6 to be similar in most of the tested brain areas of mice with high (HAB) versus normal (NAB) anxiety-related behavior, we observed distinctly altered regulation of SNF2H in the amygdala, and of CHD3 and CHD5 in the ventral hippocampus. In particular, CHD3 and CHD5 exhibited altered expression of protein but not of mRNA in HAB mice. Since both proteins are components of NuRD-like complexes, these results may indicate an impaired equilibrium between different NuRD-like complexes in the ventral hippocampus. Overall, our data provide novel evidence for localized differences of specific ATP-dependent chromatin remodeling factors in mice with high trait anxiety that may ultimately contribute to altered transcriptional programs resulting in the manifestation of pathological anxiety.
authors.affiliation: Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wille
authors.affiliation: Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Amort
authors.affiliation: Department of Pharmacology and Toxicology, Institute Pharmacy, Center for Molecular Biosciences (CMBI), Leopold-Franzens University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.affiliation: Department of Pharmacology and Toxicology, Institute Pharmacy, Center for Molecular Biosciences (CMBI), Leopold-Franzens University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. Electronic address: simone.sartori@uibk.ac.at.
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sartori
authors.affiliation: Division of Molecular Biology, Biocenter, Medical University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. Electronic address: alexandra.lusser@i-med.ac.at.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lusser
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D010551:Personality / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity
chemical_list: D015820:Cadherins; C501012:Cdh7 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D012333:RNA, Messenger; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C498725:Smarca5 protein, mouse; D004265:DNA Helicases; C583981:Chd5 protein, mouse
keywords: Emotion; Epigenetics; Fear; HAB mouse; NuRD complex; Nucleosome modification