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Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model
Hwayoung Lee,Jiyun Im,Hansol Won,Wooyoung Nam,Young Ock Kim,Sang Won Lee,Sanghyun Lee,Ik-Hyun Cho,Hyung-Ki Kim,Jun-Tack Kwon,Hak-Jae Kim 대한생리학회-대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.13 No.1
Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.
Effects of tianeptine on symptoms of fibromyalgia via BDNF signaling in a fibromyalgia animal model
Lee, Hwayoung,Im, Jiyun,Won, Hansol,Nam, Wooyoung,Kim, Young Ock,Lee, Sang Won,Lee, Sanghyun,Cho, Ik-Hyun,Kim, Hyung-Ki,Kwon, Jun-Tack,Kim, Hak-Jae The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.4
Previous reports have suggested that physical and psychological stresses may trigger fibromyalgia (FM). Stress is an important risk factor in the development of depression and memory impairments. Antidepressants have been used to prevent stress-induced abnormal pain sensation. Among various antidepressants, tianeptine has been reported to be able to prevent neurodegeneration due to chronic stress and reverse decreases in hippocampal volume. To assess the possible effect of tianeptine on FM symptoms, we constructed a FM animal model induced by restraint stress with intermittent cold stress. All mice underwent nociceptive assays using electronic von Frey anesthesiometer and Hargreaves equipment. To assess the relationship between tianeptine and expression levels of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and phosphorylated cAMP response element-binding protein (p-CREB), western blotting and immunohistochemistry analyses were performed. In behavioral analysis, nociception tests showed that pain threshold was significantly decreased in the FM group compared to that in the control group. Western blot and immunohistochemical analyses of medial prefrontal cortex (mPFC) and hippocampus showed downregulation of BDNF and p-CREB proteins in the FM group compared to the control group. However, tianeptine recovered these changes in behavioral tests and protein level. Therefore, this FM animal model might be useful for investigating mechanisms linking BDNF-CREB pathway and pain. Our results suggest that tianeptine might potentially have therapeutic efficacy for FM.
Kim, Hak-Jae,Won, Hansol,Im, Jiyun,Lee, Hwayoung,Park, Jiwoo,Lee, Sanghyun,Kim, Young-Ock,Kim, Hyung-Ki,Kwon, Jun-Tack SPANDIDOS PUBLICATIONS 2018 MOLECULAR MEDICINE REPORTS Vol.18 No.4
<P>To understand maternal immune activation (MIA) during prenatal development, the synthetic double-stranded RNA polyriboinosinic-polyribocytidylic acid [poly(I:C)] has been widely used in animal models to induce behavioral deficits similar to those in schizophrenia and other psychotic disorders. <I>Panax ginseng</I> C.A. Meyer (PG) extract is widely used to treat various kinds of nervous system disorders in Asia particularly China and Korea. The present study aimed to examine the effects of PG extract on MIA offspring using behavioral activity tests and protein expression analyses. Pregnant mice were exposed to poly(I:C) (5 mg/kg) or vehicle treatment on gestation day 9, and the resulting MIA offspring were subjected to vehicle or PG (300 mg/kg) treatment. In the acoustic startle response test, MIA-induced sensorimotor gating deficit was ameliorated by PG. The majority of behavioral parameters measured in the social interaction (non-aggressive or/and aggressive pattern), open field (number/duration of behavior) and forced swimming test (immobility behavior) were significantly altered in the MIA offspring. Western blot and immunohistochemical analyses of the medial prefrontal cortex indicated that the expression levels of certain neurodevelopmental proteins, including dihydropyrimidinase-related 2, LIM and SH3 domain 1, neurofilament medium, and discs large homolog 4, were decreased in the untreated MIA offspring, whereas PG treatment improved behavioral impairments and increased neurodevelopmental protein expression in MIA offspring. These results suggested that PG may be useful in neurodevelopmental disorder therapy, including psychiatric disorders such as schizophrenia, owing to its antipsychotic effects.</P>
Prognostic value of CAPZA1 overexpression in gastric cancer
LEE, YOUNG-JOON,JEONG, SANG-HO,HONG, SOON-CHAN,CHO, BOK-IM,HA, WOO-SONG,PARK, SOON-TAE,CHOI, SANG-KYUNG,JUNG, EUN-JUNG,JU, YOUNG-TAE,JEONG, CHI-YOUNG,KIM, JAE WON,LEE, CHANG WON,YOO, JIYUN,KO, GYUNG H D.A. Spandidos 2013 International journal of oncology Vol.42 No.5
<P>F-actin capping protein α1 subunit (CAPZA1) was previously identified in a proteomic analysis of human gastric cancer clinical specimens and selected for further study. The association between CAPZA1 overexpression, detected by immunohistochemistry, and clinicopathological features including survival were evaluated. <I>In vitro</I> gain-of-function and loss-of-function approaches were utilized to assess the function of CPAZA1 in malignancy. Univariate analysis revealed that poorly differentiated disease, according to the World Health Organization (WHO) classification, advanced T stage, positive lymph nodes, high TNM stage, D2 lymph node dissection, adjuvant chemotherapy and CAPZA1 underexpression were significantly associated with cancer-related death (p<0.05); however, only high TNM stage remained significantly associated by multivariate analysis (p<0.01). CAPZA1 overexpression was associated with well differentiated histology, smaller tumor size, lower T stage, absence of lymph node metastasis, lower TNM stage, lower recurrence rate and longer survival time, compared to CAPZA1 underexpression. <I>In vitro</I>, forced expression of CAPZA1 caused a significant decrease in gastric cancer cell migration and invasion, whereas CAPZA1 depletion had the opposite effect. The present study suggests that CAPZA1 could be a marker of good prognosis in gastric cancer and shows that CAPZA1 is associated with decreased cancer cell migration and invasion.</P>
Jeong, Sang-Ho,Ko, Gyung Hyuck,Cho, Young Hyun,Lee, Young-Joon,Cho, Bok-Im,Ha, Woo-Song,Choi, Sang-Kyung,Kim, Jae Won,Lee, Chang Won,Heo, Yoon Seok,Shin, Seok Hwan,Yoo, Jiyun,Hong, Soon-Chan Saikon Pub. Co 2012 TUMOR BIOLOGY Vol.33 No.6
<P>Inorganic pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate to form orthophosphate. Pyrophosphate can substitute for ATP under certain circumstances. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer, and PPase was identified as a potential gastric tumor-specific marker; it was therefore selected for further study. Clinicopathological analysis, using proteomic analysis and immunohistochemistry, was used to validate PPase as a prognostic marker in gastric cancers. Proteomic analysis showed that PPase was overexpressed in patients with lymph node (LN) metastases and high tumor node metastasis (TNM) stages (p < 0.05). Based on immunohistochemistry, patients whose tumors overexpressed PPase had higher T stages, LN metastasis, a higher TNM stage, a higher cancer recurrence rate, and shorter survival times than patients whose tumors exhibited PPase underexpression (p < 0.05). Gain-of-function and loss-of-function approaches were employed to examine the malignant phenotypes of PPase-overexpressing or PPase-depleted cells. A decrease in PPase expression caused a significant decrease in gastric cancer cell migration and invasion in vitro, whereas forced overexpression of PPase enhanced migration but not invasion. Our findings indicate that PPase is involved in gastric tumor progression and that PPase may be a useful marker for poor prognosis of human gastric cancers.</P>