scholarly journals c-Fos-MMP-9 pathway in central amygdala mediates approach motivation but not reward consumption

2020 ◽  
Author(s):  
T. Lebitko ◽  
J. Dzik ◽  
J. Jędrzejewska-Szmek ◽  
M. Chaturvedi ◽  
T. Jaworski ◽  
...  

AbstractAlthough impairments of motivational and consummatory aspects of reward behavior are core symptoms of several psychiatric disorders, the underlying neural and molecular mechanisms remain poorly understood. Here we report that blocking either c-Fos or matrix metalloproteinase 9 in the central amygdala disrupts approach motivation and appetitive discrimination learning, but not reward consumption. Further, we show that manipulation of c-Fos-MMP-9 pathway does not affect aversive motivation and learning. These findings reveal molecular mechanism of motivational anhedonia.

2017 ◽  
Vol 81 (11) ◽  
pp. 907-917 ◽  
Author(s):  
Marzena Stefaniuk ◽  
Anna Beroun ◽  
Tomasz Lebitko ◽  
Olga Markina ◽  
Szymon Leski ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Chao-Bin Yeh ◽  
Ming-Ju Hsieh ◽  
Yih-Shou Hsieh ◽  
Ming-Hsien Chien ◽  
Pen-Yuan Lin ◽  
...  

High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. Previous studies have identified thatTerminalia catappaleaf extracts (TCE) exert hepatoprotective, antioxidative, antiinflammatory, anticancer, and antimetastatic activities. However, the effects of TCE on HCC and the underlying molecular mechanisms of its activities have yet to be fully elucidated. The present study's findings demonstrate that TCE concentration dependently inhibits human HCC migration/invasion. Zymographic and western blot analyses revealed that TCE inhibited the activities and expression of matrix metalloproteinase-9 (MMP-9). Assessment of mRNA levels, using reverse transcriptase polymerase chain reaction (PCR) and real-time PCR, and promoter assays confirmed the inhibitory effects of TCE on MMP-9 expression in HCC cells. The inhibitory effects of TCE on MMP-9 proceeded by upregulating tissue inhibitor of metalloproteinase-1 (TIMP-1), as well as suppressing nuclear translocation and DNA binding activity of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) on the MMP-9 promoter in Huh7 cells. In conclusion, TCE inhibits MMP-9 expression and HCC cell metastasis and, thus, has potential use as a chemopreventive agent. Its inhibitory effects are associated with downregulation of the binding activities of the transcription factors NF-κB and AP-1.


2009 ◽  
Vol 219 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Christine Jespersen ◽  
Anke Doller ◽  
El-Sayed Akool ◽  
Malte Bachmann ◽  
Roswitha Müller ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249544
Author(s):  
Rana Al-Sadi ◽  
Jessica Engers ◽  
Mohammad Haque ◽  
Steven King ◽  
Deemah Al-Omari ◽  
...  

Background Matrix Metalloproteinase-9 (MMP-9) has been shown to play a key role in mediating inflammation and tissue damage in inflammatory bowel disease (IBD). In patients with IBD, the intestinal tight junction (TJ) barrier is compromised as characterized by an increase in intestinal permeability. MMP-9 is elevated in intestinal tissue, serum and stool of patients with IBD. Previous studies from our laboratory showed that MMP-9 causes an increase in intestinal epithelial TJ permeability and that the MMP-9 induced increase in intestinal permeability is an important pathogenic factor contributing to the development of intestinal inflammation in IBD. However, the intracellular mechanisms that mediate the MMP-9 modulation of intestinal barrier function remain unclear. Aims The main aim of this study was to further elucidate the molecular mechanisms involved in MMP-9 induced increase in intestinal epithelial TJ permeability using Caco-2 monolayers as an in-vitro model system. Results MMP-9 induced increase in Caco-2 TJ permeability was associated with activation and cytoplasmic-to-nuclear translocation of NF-κB p65. Knocking-down NF-κB p65 by siRNA transfection prevented the MMP-9 induced expression of the NF-κB target gene IL-8, myosin light chain kinase (MLCK) protein expression, and subsequently prevented the increase in Caco-2 TJ permeability. In addition, the effect of MMP-9 on Caco-2 intestinal epithelial TJ barrier function was not mediated by apoptosis or necrosis. Conclusion Our data show that the MMP-9 induced disruption of Caco-2 intestinal epithelial TJ barrier function is regulated by NF-κB pathway activation of MLCK.


2013 ◽  
Vol 33 (36) ◽  
pp. 14591-14600 ◽  
Author(s):  
E. Knapska ◽  
V. Lioudyno ◽  
A. Kiryk ◽  
M. Mikosz ◽  
T. Gorkiewicz ◽  
...  

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