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MARCKSL1 Regulates Spine Formation in the Amygdala and Controls the Hypothalamic-Pituitary-Adrenal Axis and Anxiety-Like Behaviors.


ABSTRACT: 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.

SUBMITTER: Tanaka T 

PROVIDER: S-EPMC5952351 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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MARCKSL1 Regulates Spine Formation in the Amygdala and Controls the Hypothalamic-Pituitary-Adrenal Axis and Anxiety-Like Behaviors.

Tanaka Takashi T   Shimizu Shoko S   Ueno Masaki M   Fujihara Yoshitaka Y   Ikawa Masahito M   Miyata Shingo S  

EBioMedicine 20180319


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 co  ...[more]

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