scholarly journals Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Lu ◽  
Jia Liang ◽  
Jun-Ren Wang ◽  
Li Hu ◽  
Ya Tu ◽  
...  

Extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway has been implicated in the pathogenesis of depression. There is growing evidence that acupuncture in traditional Chinese medicine has antidepressant-like effect. However, the effect of acupuncture on ERK-CREB pathway remains unknown. In our study, the antidepressant-like effect of acupuncture treatment was measured by sucrose intake test and open field test in rats exposed to chronic unpredictable mild stress (CUMS) for 4 weeks. The protein levels of ERK1/2, CREB, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated CREB (p-CREB) in the hippocampus (HP) and prefrontal cortex (PFC) were examined by Western blot analysis. Our results showed that CUMS rats exhibited the reduction in behavioral activities, whereas acupuncture stimulation at acupoints Baihui (Du20) and Neiguan (PC6) reversed the behavioral deficit. In addition, exposure to CUMS resulted in the decrease of p-ERK1/2 and p-CREB in the HP and PFC. Acupuncture increased the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the HP and PFC. Our study suggested that one potential way, by which acupuncture had antidepressant-like effect, might be mediated by activating the ERK-CREB pathway in the brain.

2014 ◽  
Vol 9 (10) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Mitsuhiro Nakamura ◽  
Tomoko Suzuki ◽  
Mai Takagi ◽  
Hirotoshi Tamura ◽  
Toshiya Masuda

Bioactive compounds from citrus fruits contribute many benefits to human health. Extracellular signal-regulated kinase (ERK) signaling plays an important role in the regulation of multiple cellular processes. Activation of the ERK-cAMP response element binding protein (CREB) signaling is required for long-term memory formation. In this study, auraptene, phellopterin, thymol, coniferyl alcohol 9-methyl ether and methyl ferulate were isolated from Citrus junos. Among the five compounds isolated, auraptene and phellopterin increased the phosphorylation of ERK and CREB. This study provides, to our knowledge, the first evidence that phellopterin potently stimulates the phosphorylation of ERK and CREB. Phellopterin could be a novel neuroprotective agent.


1999 ◽  
Vol 13 (8) ◽  
pp. 1338-1352
Author(s):  
W. Rachel Duan ◽  
Jennifer L. Shin ◽  
J. Larry Jameson

Abstract Estradiol acts on the hypothalamus and pituitary gland to modulate the synthesis and secretion of gonadotropins. We recently reported that GnRH-induced transcription of the human gonadotropin α-gene promoter is increased markedly in transfected pituitary cells derived from animals treated with estradiol. Because the cAMP response element binding (CREB) protein plays an important role in the transcriptional regulation of this promoter and is highly regulated by posttranslational phosphorylation, we hypothesized that it might serve as a target for estradiol-induced sensitivity to GnRH. In this study, we assessed the roles of estradiol and GnRH in the regulation of CREB phosphorylation in the rat pituitary. Using an antibody that specifically recognizes phosphorylated CREB (pCREB), we found that the pituitary content of pCREB was inversely related to the level of estradiol during the estrous cycle. Ovariectomy increased the level of pCREB, and treatment with estradiol for 10 days decreased the content of pCREB dramatically (93% inhibition). A similar reduction of pCREB was seen when ovariectomized rats were treated with a GnRH receptor antagonist for 10 days. This result indicates that the ovariectomy-induced increase in pCREB is GnRH-dependent. In αT3 gonadotrope cells, estradiol had no direct effect on CREB phosphorylation, whereas GnRH increased CREB phosphorylation 4- to 5-fold within 5 min. We conclude that estradiol inhibits CREB phosphorylation in the gonadotrope, probably by inhibiting GnRH production. The estradiol-induced decrease in CREB phosphorylation is proposed to lower basalα -promoter activity and increase its responsiveness to GnRH. (Molecular Endocrinology 13: 1338–1352, 1999)


1998 ◽  
Vol 61 (1-2) ◽  
pp. 69-77 ◽  
Author(s):  
Tatsuo Suzuki ◽  
Nobuteru Usuda ◽  
Hiroshi Ishiguro ◽  
Shigehisa Mitake ◽  
Toshiharu Nagatsu ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Yul Kim ◽  
Yongtaek Seo ◽  
Chan Lee ◽  
Gyu Hwan Park ◽  
Jung-Hee Jang

We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day). To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF). The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB) signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Congcong Sun ◽  
Yun Wang ◽  
Mingshu Mo ◽  
Chengyuan Song ◽  
Xingbang Wang ◽  
...  

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson’s disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.


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