Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype

Xingshun Xu, Hao Yang, Yung Feng Lin, Xiang Li, Austin Cape, Kerry J. Ressler, Shihua Li, Xiao Jiang Li

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Recent studies suggest that the human Abelson helper integration site-1 (AHI1) gene on chromosome 6 is associated with susceptibility to schizophrenia and autism, two common neuropsychological disorders with depression symptoms. Mouse Ahi1 protein is abundant in the hypothalamus and amygdala, which are important brain regions for controlling emotion. However, the neuronal function of Ahi1 remains unclear. With the Cre-loxP system, we created a mouse model that selectively reduces Ahi1 expression in neuronal cells. Mice with neuronal Ahi1 deficiency show reduced TrkB level in the brain and depressive phenotypes, which can be alleviated by antidepressant drugs or by overexpression of TrkB in the amygdala. Ahi1 deficiency promotes the degradation of endocytic TrkB and reduces TrkB signaling in neuronal cells. Our findings suggest that impaired endocytic sorting and increased degradation of TrkB can induce depression and that this impaired pathway may serve as a previously uncharacterized therapeutic target for depression.

Original languageEnglish
Pages (from-to)19126-19131
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number44
DOIs
Publication statusPublished - Nov 2 2010
Externally publishedYes

Fingerprint

Depression
Amygdala
Phenotype
Chromosomes, Human, Pair 6
Brain
Autistic Disorder
Antidepressive Agents
Hypothalamus
Schizophrenia
Emotions
Genes
Mouse Ahi1 protein
Therapeutics

Keywords

  • Endocytosis
  • Neuropathology
  • Neuropsychiatric
  • Neurotrophic
  • Trafficking

ASJC Scopus subject areas

  • General

Cite this

Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype. / Xu, Xingshun; Yang, Hao; Lin, Yung Feng; Li, Xiang; Cape, Austin; Ressler, Kerry J.; Li, Shihua; Li, Xiao Jiang.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 44, 02.11.2010, p. 19126-19131.

Research output: Contribution to journalArticle

Xu, Xingshun ; Yang, Hao ; Lin, Yung Feng ; Li, Xiang ; Cape, Austin ; Ressler, Kerry J. ; Li, Shihua ; Li, Xiao Jiang. / Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 44. pp. 19126-19131.
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