title: Loss of Ahi1 impairs neurotransmitter release and causes depressive behaviors in mice.
abstract: Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1) deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO) mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets.
authors.affiliation: Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Xuanchen
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Zhai
authors.affiliation: The Institute for Fetology, the First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: The Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Neurology, Suzhou Kowloon Hospital, Suzhou City, Jiangsu Province, China.
authors.forename: Jizhen
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, China; The Institute of Neuroscience, Soochow University, Suzhou City, Jiangsu Province, China.
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001522:Behavior, Animal; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012701:Serotonin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C465818:Ahi1 protein, mouse; D018377:Neurotransmitter Agents; D011518:Proto-Oncogene Proteins; D012701:Serotonin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007099:Imipramine; D004298:Dopamine