Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characte...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 28; pp. 11378 - 11383
Main Authors:	Son, Hyeon, Banasr, Mounira, Choi, Miyeon, Chae, Seung Yeon, Licznerski, Pawel, Lee, Boyoung, Voleti, Bhavya, Li, Nanxin, Lepack, Ashley, Fournier, Neil M, Lee, Ka Rim, Lee, In Young, Kim, Juhyun, Kim, Joung-Hun, Kim, Yong Ho, Jung, Sung Jun, Duman, Ronald S
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 10-07-2012 National Acad Sciences
Subjects:	Anhedonia Animals Antidepressants Antidepressive Agents - pharmacology anxiety atrophy Behavioral neuroscience Biological Sciences Brain Brain-Derived Neurotrophic Factor - metabolism dendrites Dendrites - physiology Depressive Disorder, Major - drug therapy Depressive Disorder, Major - metabolism Depressive Disorder, Major - physiopathology Depressive disorders Disease Models, Animal Gene expression genes Genetic variation GPI-Linked Proteins - metabolism Hippocampus Hippocampus - metabolism Hippocampus - physiology Learning - physiology Male Medical treatment memory Memory - physiology Mental depression Messenger RNA Neuronal Plasticity Neurons Neurons - metabolism Neurons - physiology Neuropeptides - metabolism Neuroplasticity Proteins Rats Rats, Sprague-Dawley Stress Stress, Psychological Synapses - physiology
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Summary:	Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.
Bibliography:	http://dx.doi.org/10.1073/pnas.1201191109 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: H.S. and R.S.D. designed research; H.S., M.B., M.C., S.Y.C., P.L., B.L., B.V., N.L., A.L., N.M.F., K.R.L., I.Y.L., Y.H.K., and S.J.J. performed research; J.K. and J.-H.K. contributed new reagents/analytic tools; and H.S. and R.S.D. wrote the paper. Edited* by Bruce S. McEwen, The Rockefeller University, New York, NY, and approved May 28, 2012 (received for review January 23, 2012)
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.1201191109