scholarly journals GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression

Oncotarget ◽  
2017 ◽  
Vol 8 (22) ◽  
pp. 35933-35945 ◽  
Author(s):  
Zhaoming Zhu ◽  
Guangyan Wang ◽  
Ke Ma ◽  
Shan Cui ◽  
Jin-Hui Wang
2015 ◽  
Author(s):  
Kerin K Higa ◽  
Baohu Ji ◽  
Mahalah R Buell ◽  
Risbrough B Victoria ◽  
Susan B Powell ◽  
...  

Ketamine produces schizophrenia-like behavioral phenotypes in healthy people. Prolonged ketamine effects and exacerbation of symptoms were observed in schizophrenia patients after administration of ketamine. More recently, ketamine has been used as a potent antidepressant to treat patients with major depression. The genes and neurons that regulate behavioral responses to ketamine, however, remain poorly understood. Our previous studies found that Sp4 hypomorphic mice displayed several behavioral phenotypes relevant to psychiatric disorders, consistent with human SP4 gene associations with schizophrenia, bipolar, and major depression. Among those behavioral phenotypes, hypersensitivity to ketamine-induced hyperlocomotion has been observed in Sp4 hypomorphic mice. Here, we report differential genetic restoration of Sp4 expression in forebrain excitatory neurons or GABAergic neurons in Sp4 hypomorphic mice and the effects of these restorations on different behavioral phenotypes. Restoration of Sp4 in forebrain excitatory neurons did not rescue deficient sensorimotor gating, fear learning, or ketamine-induced hyperlocomotion. Restoration of Sp4 in forebrain GABAergic neurons, however, rescued ketamine-induced hyperlocomotion, but did not rescue deficient sensorimotor gating or fear learning. Our studies suggest that the Sp4 gene in forebrain GABAergic neurons plays an essential role in regulating some behavioral responses to ketamine.


2002 ◽  
Vol 83 (4) ◽  
pp. 895-903 ◽  
Author(s):  
Simona Scheggi ◽  
Benedetta Leggio ◽  
Flavio Masi ◽  
Silvia Grappi ◽  
Carla Gambarana ◽  
...  

2020 ◽  
Vol 295 (20) ◽  
pp. 6831-6848 ◽  
Author(s):  
Li Guo ◽  
Zhaoming Zhu ◽  
Guangyan Wang ◽  
Shan Cui ◽  
Meng Shen ◽  
...  

Major depression is a prevalent affective disorder characterized by recurrent low mood. It presumably results from stress-induced deteriorations of molecular networks and synaptic functions in brain reward circuits of genetically-susceptible individuals through epigenetic processes. Epigenetic regulator microRNA-15b inhibits neuronal progenitor proliferation and is up-regulated in the medial prefrontal cortex of mice that demonstrate depression-like behavior, indicating the contribution of microRNA-15 to major depression. Using a mouse model of major depression induced by chronic unpredictable mild stress (CUMS), here we examined the effects of microRNA-15b on synapses and synaptic proteins in the nucleus accumbens of these mice. The application of a microRNA-15b antagomir into the nucleus accumbens significantly reduced the incidence of CUMS-induced depression and reversed the attenuations of excitatory synapse and syntaxin-binding protein 3 (STXBP3A)/vesicle-associated protein 1 (VAMP1) expression. In contrast, the injection of a microRNA-15b analog into the nucleus accumbens induced depression-like behavior as well as attenuated excitatory synapses and STXBP3A/VAMP1 expression similar to the down-regulation of these processes induced by the CUMS. We conclude that microRNA-15b-5p may play a critical role in chronic stress-induced depression by decreasing synaptic proteins, innervations, and activities in the nucleus accumbens. We propose that the treatment of anti-microRNA-15b-5p may convert stress-induced depression into resilience.


2008 ◽  
Vol 165 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Christopher S. Monk ◽  
Rachel G. Klein ◽  
Eva H. Telzer ◽  
Elizabeth A. Schroth ◽  
Salvatore Mannuzza ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-26 ◽  
Author(s):  
Hui Qiao ◽  
Ming-Xing Li ◽  
Chang Xu ◽  
Hui-Bin Chen ◽  
Shu-Cheng An ◽  
...  

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.


Stress ◽  
2013 ◽  
Vol 17 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Jean-François Poulin ◽  
Sylvie Laforest ◽  
Guy Drolet

2010 ◽  
Vol 67 (5) ◽  
pp. 465-470 ◽  
Author(s):  
Dorota Maciag ◽  
Jonathan Hughes ◽  
Gillian O'Dwyer ◽  
Yilianys Pride ◽  
Craig A. Stockmeier ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document