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Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3.
Psychoneuroendocrinology 2018; 92:13-20P

Abstract

The LIM domain only protein LMO3 is a transcriptional regulator that has been shown to regulate several behavioral responses to alcohol. Specifically, Lmo3 null (Lmo3Z) mice consume more ethanol in a binge-drinking test and show enhanced ethanol-induced sedation. Due to the high comorbidity of alcohol use and anxiety, we investigated anxiety-like behavior in Lmo3Z mice. Lmo3Z mice spent more time in the open arms of the elevated plus maze compared with their wild-type littermates, but the effect was confounded by reduced locomotor activity. To verify the anxiety phenotype in the Lmo3Z mice, we tested them for novelty-induced hypophagia and found that they also showed reduced anxiety in this test. We next explored the mechanism by which LMO3 might regulate anxiety by measuring mRNA and protein levels of corticotropin releasing factor (encoded by the Crh gene) and its receptor type 1 (Crhr1) in Lmo3Z mice. Reduced Crhr1 mRNA and protein was evident in the basolateral amygdala (BLA) of Lmo3Z mice. To examine whether Lmo3 in the amygdala is important for anxiety-like behavior, we locally reduced Lmo3 expression in the BLA of wild type mice using a lentiviral vector expressing a short hairpin RNA targeting the Lmo3 transcript. Mice with Lmo3 knockdown in the BLA exhibited decreased anxiety-like behavior relative to control mice. These results suggest that Lmo3 promotes anxiety-like behavior specifically in the BLA, possibly by altering Crhr1 expression. This study is the first to support a role for Lmo3 in anxiety-like behavior.

Authors+Show Affiliations

Center for Alcohol Research in Epigenetics and Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612 USA; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, IL 60612 USA. Electronic address: savarese@ohsu.edu.Center for Alcohol Research in Epigenetics and Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612 USA. Electronic address: alasek@uic.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29609111

Citation

Savarese, Antonia, and Amy W. Lasek. "Regulation of Anxiety-like Behavior and Crhr1 Expression in the Basolateral Amygdala By LMO3." Psychoneuroendocrinology, vol. 92, 2018, pp. 13-20.
Savarese A, Lasek AW. Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3. Psychoneuroendocrinology. 2018;92:13-20.
Savarese, A., & Lasek, A. W. (2018). Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3. Psychoneuroendocrinology, 92, pp. 13-20. doi:10.1016/j.psyneuen.2018.03.016.
Savarese A, Lasek AW. Regulation of Anxiety-like Behavior and Crhr1 Expression in the Basolateral Amygdala By LMO3. Psychoneuroendocrinology. 2018;92:13-20. PubMed PMID: 29609111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of anxiety-like behavior and Crhr1 expression in the basolateral amygdala by LMO3. AU - Savarese,Antonia, AU - Lasek,Amy W, Y1 - 2018/03/27/ PY - 2017/12/29/received PY - 2018/02/20/revised PY - 2018/03/25/accepted PY - 2018/4/3/pubmed PY - 2019/2/16/medline PY - 2018/4/3/entrez KW - Anxiety KW - Basolateral amygdala KW - CRF KW - CRF1 receptor KW - CRH KW - LMO3 SP - 13 EP - 20 JF - Psychoneuroendocrinology JO - Psychoneuroendocrinology VL - 92 N2 - The LIM domain only protein LMO3 is a transcriptional regulator that has been shown to regulate several behavioral responses to alcohol. Specifically, Lmo3 null (Lmo3Z) mice consume more ethanol in a binge-drinking test and show enhanced ethanol-induced sedation. Due to the high comorbidity of alcohol use and anxiety, we investigated anxiety-like behavior in Lmo3Z mice. Lmo3Z mice spent more time in the open arms of the elevated plus maze compared with their wild-type littermates, but the effect was confounded by reduced locomotor activity. To verify the anxiety phenotype in the Lmo3Z mice, we tested them for novelty-induced hypophagia and found that they also showed reduced anxiety in this test. We next explored the mechanism by which LMO3 might regulate anxiety by measuring mRNA and protein levels of corticotropin releasing factor (encoded by the Crh gene) and its receptor type 1 (Crhr1) in Lmo3Z mice. Reduced Crhr1 mRNA and protein was evident in the basolateral amygdala (BLA) of Lmo3Z mice. To examine whether Lmo3 in the amygdala is important for anxiety-like behavior, we locally reduced Lmo3 expression in the BLA of wild type mice using a lentiviral vector expressing a short hairpin RNA targeting the Lmo3 transcript. Mice with Lmo3 knockdown in the BLA exhibited decreased anxiety-like behavior relative to control mice. These results suggest that Lmo3 promotes anxiety-like behavior specifically in the BLA, possibly by altering Crhr1 expression. This study is the first to support a role for Lmo3 in anxiety-like behavior. SN - 1873-3360 UR - https://www.unboundmedicine.com/medline/citation/29609111/Regulation_of_anxiety_like_behavior_and_Crhr1_expression_in_the_basolateral_amygdala_by_LMO3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4530(17)31654-2 DB - PRIME DP - Unbound Medicine ER -