Azita Minaei1, Hashem Haghdoost-Yazdi2. 1. Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. 2. Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address: hhaghdoost@yahoo.com.
Abstract
BACKGROUND: Studies have shown that dexmedetomidine (DEX), a potent α2-adrenoceptors agonist provides neuroprotection through suppression of inflammatory response. In present study, we examined effect of DEX and its underlying mechanisms on the induction and progress of 6-OHDA- induced Parkinsonism in rat. MATERIAL AND METHODS: The 6-OHDA was injected into the medial forebrain bundle of right hemisphere by stereotaxic surgery and then, behavioral tests carried out within second, fourth, sixth and eighth weeks post-surgery. All treatments were started before the toxin and continued to eight weeks afterwards. Striatal levels of dopamine, TNF-α and IL-6 were measured within the eighth week after the toxin by enzyme-linked immunosorbent assay kits. RESULTS: DEX at dose of 50 μg/kg attenuated significantly the intensity of 6-OHDA- induced behavioral symptoms in the second week post-surgery. DEX also attenuated remarkably 6-OHDA- induced reduction in striatal dopamine level. These effects were also observed in rats treated by both DEX and yohimbine (YOH), a selective α2-adrenoceptors antagonist but were not observed in rats treated by both of DEX and glibenclamide (Glib), an ATP-sensitive potassium (KATP) channels blocker. DEX also reversed the progressive increase in intensity of the behavioral symptoms and reversed 6-OHDA- induced overproduction of TNF-α and IL-6. These effects were reversed by YOH but not Glib. CONCLUSION: Our findings indicate that DEX attenuates the induction and reverses the progress of 6-OHDA- induced Parkinsonism through activation of KATP channels and α2-adrenoceptors, respectively. Through activation of α2-adrenoceptors, DEX also exerts anti-inflammatory effect which is possibly another mechanism underlying the DEX's antiparkinsonism effect.
BACKGROUND: Studies have shown that dexmedetomidine (DEX), a potent α2-adrenoceptors agonist provides neuroprotection through suppression of inflammatory response. In present study, we examined effect of DEX and its underlying mechanisms on the induction and progress of 6-OHDA- induced Parkinsonism in rat. MATERIAL AND METHODS: The 6-OHDA was injected into the medial forebrain bundle of right hemisphere by stereotaxic surgery and then, behavioral tests carried out within second, fourth, sixth and eighth weeks post-surgery. All treatments were started before the toxin and continued to eight weeks afterwards. Striatal levels of dopamine, TNF-α and IL-6 were measured within the eighth week after the toxin by enzyme-linked immunosorbent assay kits. RESULTS:DEX at dose of 50 μg/kg attenuated significantly the intensity of 6-OHDA- induced behavioral symptoms in the second week post-surgery. DEX also attenuated remarkably 6-OHDA- induced reduction in striatal dopamine level. These effects were also observed in rats treated by both DEX and yohimbine (YOH), a selective α2-adrenoceptors antagonist but were not observed in rats treated by both of DEX and glibenclamide (Glib), an ATP-sensitive potassium (KATP) channels blocker. DEX also reversed the progressive increase in intensity of the behavioral symptoms and reversed 6-OHDA- induced overproduction of TNF-α and IL-6. These effects were reversed by YOH but not Glib. CONCLUSION: Our findings indicate that DEX attenuates the induction and reverses the progress of 6-OHDA- induced Parkinsonism through activation of KATP channels and α2-adrenoceptors, respectively. Through activation of α2-adrenoceptors, DEX also exerts anti-inflammatory effect which is possibly another mechanism underlying the DEX's antiparkinsonism effect.