Adaptor Protein APPL2 Affects Adult Antidepressant Behaviors and Hippocampal Neurogenesis via Regulating the Sensitivity of Glucocorticoid Receptor

Chong Gao, Xingmiao Chen, Aimin Xu, King Yip Cheng, Jiangang Shen

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)


Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins involved in regulating many biological activities and processes. The newly identified metabolic factor APPL2 showed the potentials to modulate cell growth, but whether APPL2 could affect adult neurogenesis and animal mood behaviors remains unknown. In the present study, APPL2 transgenic (Tg) mice and wild-type littermates were used for testing our hypothesis that APPL2 could affect glucocorticoid receptor (GR) signaling and modulate hippocampal neurogenesis, which contributes to depressive and anxiety behaviors. Compared with WT littermates, APPL2 Tg mice had enhanced GR phosphorylation under basic condition but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. APPL2 Tg mice had decreased hippocampal neurogenesis that was reversed by GR antagonist RU486. APPL2 Tg mice also showed the impaired hippocampal neurogenesis and presented the depressive and anxiety behaviors. In conclusion, APPL2 could be an important regulator for adult neurogenesis. APPL2 overexpression could blunt the activation of glucocorticoid receptor when undergoing environmental stress. Our study suggests that APPL2 might be a new therapeutic target for mental disorders.
Original languageEnglish
Pages (from-to)5537-5547
Number of pages11
JournalMolecular Neurobiology
Issue number7
Publication statusPublished - 1 Jul 2018


  • Adult neurogenesis
  • APPL2
  • Behavior
  • Depression
  • Glucocorticoid receptor
  • Hippocampus

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

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