MARCKSL1 Regulates Spine Formation in the Amygdala and Controls the Hypothalamic-Pituitary-Adrenal Axis and Anxiety-Like Behaviors
Takashi Tanaka,
Shoko Shimizu,
Masaki Ueno,
Yoshitaka Fujihara,
Masahito Ikawa,
Shingo Miyata
Affiliations
Takashi Tanaka
Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan; Department of Anatomy II, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan; Corresponding author at: Department of Anatomy II, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa 920-0293, Japan.
Shoko Shimizu
Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
Masaki Ueno
Brain Research Institute, Niigata University, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8585, Japan; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, United States
Yoshitaka Fujihara
Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Masahito Ikawa
Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan; Animal Resource Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan
Shingo Miyata
Division of Molecular Brain Science, Research Institute of Traditional Asian Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
Abnormalities in limbic neural circuits have been implicated in the onset of anxiety disorders. However, the molecular pathogenesis underlying anxiety disorders remains poorly elucidated. Here, we demonstrate that myristoylated alanine-rich C-kinase substrate like 1 (MARCKSL1) regulates amygdala circuitry to control the activity of the hypothalamic-pituitary-adrenal (HPA) axis, as well as induces anxiety-like behaviors in mice. MARCKSL1 expression was predominantly localized in the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala of the adult mouse brain. MARCKSL1 transgenic (Tg) mice exhibited anxiety-like behaviors dependent on corticotropin-releasing hormone. MARCKSL1 increased spine formation in the central amygdala, and downregulation of MARCKSL1 in the amygdala normalized both increased HPA axis activity and elevated anxiety-like behaviors in Tg mice. Furthermore, MARCKSL1 expression was increased in the PFC and amygdala in a brain injury model associated with anxiety-like behaviors. Our findings suggest that MARCKSL1 expression in the amygdala plays an important role in anxiety-like behaviors. Keywords: MARCKSL1, Spine formation, Amygdala, HPA axis, Anxiety-like behaviors
