title: Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval.
abstract: The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders.
authors.affiliation: Clinic of Neurology, University of Magdeburg, D-39120 Magdeburg, Germany; Leibniz Institute of Neurobiology, D-39118 Magdeburg, Germany. Electronic address: kathrin.janitzky@med.ovgu.de.
authors.forename: K
authors.initials: K
authors.lastname: Janitzky
authors.affiliation: Institute of Anatomy, University of Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Peine
authors.affiliation: Institute of Anatomy, University of Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kröber
authors.affiliation: Department of Genetic and Behavioural Neuroscience, Gunma University, Maebashi 371-8511, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Institute of Anatomy, University of Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schwegler
authors.affiliation: Institute of Anatomy, University of Magdeburg, D-39120 Magdeburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Roskoden
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000172:deficiency* / Q000235:genetics; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008822:Mice, Transgenic; D009483:Neuropsychological Tests; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology; D010812:Physical Stimulation; D011235:Predatory Behavior; D012333:RNA, Messenger / Q000378:metabolism; D012686:Septal Nuclei / Q000503:physiopathology*; D012727:Sex Characteristics; D065853:Spatial Learning / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: BNST; CRF; GAD67 mouse; Predator odor; Spatial memory; Trimethylthiazoline