• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.361-370
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• 2017

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.

• Journal of Ginseng Research
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• 제34권3호
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• pp.246-253
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• 2010

Ginsenoside $Rg_3$ ($Rg_3$), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of $Rg_3$ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that $Rg_3$ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an $IC_{50}$ value of $28.7{\pm}7.5\;{\mu}m$. Furthermore, the $Rg_3$ treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of $Rg_3$ against 25-OH-chol-induced cytotoxicity, we also examined the effect of $Rg_3$ on intracellular $Ca^{2+}$ elevations in cultured neurons and found that $Rg_3$ treatment dose-dependently inhibited increases in intracellular $Ca^{2+}$, with an $IC_{50}$ value of $40.37{\pm}12.88\;{\mu}m$. Additionally, $Rg_3$ treatment dose-dependently inhibited apoptosis with an $IC_{50}$ of $47.3{\pm}14.2\;{\mu}m$. Finally, after confirming the protective effect of $Rg_3$ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that $Rg_3$ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that $Rg_3$-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated $Ca^{2+}$ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of $Rg_3$ against 24-OH-chol. In conclusion, $Rg_3$ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes $Rg_3$ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.