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Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome.
Psychoneuroendocrinology 2020; 111:104480P

Abstract

The highly conserved transcription factor LIM-only 3 (Lmo3) is involved in important neurodevelopmental processes in several brain areas including the amygdala, a central hub for the generation and regulation of emotions. Accordingly, a role for Lmo3 in the behavioral responses to ethanol and in the display of anxiety-like behavior in mice has been demonstrated while the potential involvement of Lmo3 in the control of mood-related behavior has not yet been explored. Using a mouse model of Lmo3 depletion (Lmo3z), we here report that genetic Lmo3 deficiency is associated with altered performance in behavioral paradigms assessing anxiety-like and depression-like traits and additionally accompanied by impairments in learned fear. Importantly, long-term potentiation (LTP) in the basolateral amygdala (BLA), a proposed cellular correlate of fear learning, is impaired in Lmo3z mice. RNA-Seq analysis of BLA tissue and gene set enrichment analysis (GSEA) of differentially expressed genes in Lmo3z mice reveals a significant overlap between genes overexpressed in Lmo3z mice and those enriched in the amygdala of a cohort of patients suffering from major depressive disorder. Consequently, we propose that Lmo3 may play a role in the regulation of gene networks that are relevant to the regulation of emotions. Future work may aid to further explore the role of Lmo3 in the pathophysiology of affective disorders and its genetic foundations.

Authors+Show Affiliations

Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Laboratory Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Core Facilities Genomics, Medical University of Vienna, Lazarettgasse 14, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria.Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstraβe 17, 1090, Vienna, Austria. Electronic address: daniela.pollak@meduniwien.ac.at.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31707294

Citation

Reisinger, Sonali N., et al. "Lmo3 Deficiency in the Mouse Is Associated With Alterations in Mood-related Behaviors and a Depression-biased Amygdala Transcriptome." Psychoneuroendocrinology, vol. 111, 2020, p. 104480.
Reisinger SN, Bilban M, Stojanovic T, et al. Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome. Psychoneuroendocrinology. 2020;111:104480.
Reisinger, S. N., Bilban, M., Stojanovic, T., Derdak, S., Yang, J., Cicvaric, A., ... Pollak, D. D. (2020). Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome. Psychoneuroendocrinology, 111, p. 104480. doi:10.1016/j.psyneuen.2019.104480.
Reisinger SN, et al. Lmo3 Deficiency in the Mouse Is Associated With Alterations in Mood-related Behaviors and a Depression-biased Amygdala Transcriptome. Psychoneuroendocrinology. 2020;111:104480. PubMed PMID: 31707294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lmo3 deficiency in the mouse is associated with alterations in mood-related behaviors and a depression-biased amygdala transcriptome. AU - Reisinger,Sonali N, AU - Bilban,Martin, AU - Stojanovic,Tamara, AU - Derdak,Sophia, AU - Yang,Jiaye, AU - Cicvaric,Ana, AU - Horvath,Orsolya, AU - Sideromenos,Spyros, AU - Zambon,Alice, AU - Monje,Francisco J, AU - Boehm,Stefan, AU - Pollak,Daniela D, Y1 - 2019/10/19/ PY - 2019/02/23/received PY - 2019/09/04/revised PY - 2019/10/11/accepted PY - 2019/11/11/pubmed PY - 2019/11/11/medline PY - 2019/11/11/entrez KW - Amygdala KW - Depression KW - Fear KW - LIM-only 3 KW - LTP KW - Lmo3 SP - 104480 EP - 104480 JF - Psychoneuroendocrinology JO - Psychoneuroendocrinology VL - 111 N2 - The highly conserved transcription factor LIM-only 3 (Lmo3) is involved in important neurodevelopmental processes in several brain areas including the amygdala, a central hub for the generation and regulation of emotions. Accordingly, a role for Lmo3 in the behavioral responses to ethanol and in the display of anxiety-like behavior in mice has been demonstrated while the potential involvement of Lmo3 in the control of mood-related behavior has not yet been explored. Using a mouse model of Lmo3 depletion (Lmo3z), we here report that genetic Lmo3 deficiency is associated with altered performance in behavioral paradigms assessing anxiety-like and depression-like traits and additionally accompanied by impairments in learned fear. Importantly, long-term potentiation (LTP) in the basolateral amygdala (BLA), a proposed cellular correlate of fear learning, is impaired in Lmo3z mice. RNA-Seq analysis of BLA tissue and gene set enrichment analysis (GSEA) of differentially expressed genes in Lmo3z mice reveals a significant overlap between genes overexpressed in Lmo3z mice and those enriched in the amygdala of a cohort of patients suffering from major depressive disorder. Consequently, we propose that Lmo3 may play a role in the regulation of gene networks that are relevant to the regulation of emotions. Future work may aid to further explore the role of Lmo3 in the pathophysiology of affective disorders and its genetic foundations. SN - 1873-3360 UR - https://www.unboundmedicine.com/medline/citation/31707294/Lmo3_deficiency_in_the_mouse_is_associated_with_alterations_in_mood-related_behaviors_and_a_depression-biased_amygdala_transcriptome L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4530(19)30171-4 DB - PRIME DP - Unbound Medicine ER -