title: Anxiety in liver X receptor β knockout female mice with loss of glutamic acid decarboxylase in ventromedial prefrontal cortex.
abstract: Anxiety disorders are the most prevalent mental disorders in adolescents in the United States. Female adolescents are more likely than males to be affected with anxiety disorders, but less likely to have behavioral and substance abuse disorders. The prefrontal cortex (PFC), amygdala, and dorsal raphe are known to be involved in anxiety disorders. Inhibitory input from the PFC to the amygdala controls fear and anxiety typically originating in the amygdala, and disruption of the inhibitory input from the PFC leads to anxiety, fear, and personality changes. Recent studies have implicated liver X receptor β (LXRβ) in key neurodevelopmental processes and neurodegenerative diseases. In the present study, we used elevated plus-maze, startle and prepulse inhibition, open field, and novel object recognition tests to evaluate behavior in female LXRβ KO (LXRβ(-/-)) mice. We found that the female LXRβ(-/-) mice were anxious with impaired behavioral responses but normal locomotion and memory. Immunohistochemistry analysis revealed decreased expression of the enzyme responsible for GABA synthesis, glutamic acid decarboxylase (65+67), in the ventromedial PFC. Expression of tryptophan hydroxylase 2 in the dorsal raphe was normal. We conclude that the anxiogenic phenotype in female LXRβ(-/-) mice is caused by reduced GABAergic input from the ventromedial PFC to the amygdala.
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA.
authors.forename: Xin-jie
authors.initials: XJ
authors.lastname: Tan
authors.forename: Yu-bing
authors.initials: YB
authors.lastname: Dai
authors.forename: Wan-fu
authors.initials: WF
authors.lastname: Wu
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
mesh_terms: D000293:Adolescent; D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology*; D005239:Fear / Q000502:physiology / Q000523:psychology; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D000071518:Liver X Receptors; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D057093:Orphan Nuclear Receptors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017397:Prefrontal Cortex / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D012737:Sex Factors; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase