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 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.
Department of Psychiatry, Yale University, New Haven, CT 06508, USA. hyeonson@hanyang.ac.kr
Hyeon
H
Son
Mounira
M
Banasr
Miyeon
M
Choi
Seung Yeon
SY
Chae
Pawel
P
Licznerski
Boyoung
B
Lee
Bhavya
B
Voleti
Nanxin
N
Li
Ashley
A
Lepack
Neil M
NM
Fournier
Ka Rim
KR
Lee
In Young
IY
Lee
Juhyun
J
Kim
Joung-Hun
JH
Kim
Yong Ho
YH
Kim
Sung Jun
SJ
Jung
Ronald S
RS
Duman
D059445:Anhedonia; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003712:Dendrites / Q000502:physiology; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological; D013569:Synapses / Q000502:physiology
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; D009479:Neuropeptides; C105161:Nrn1 protein, rat