Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron
| Autor: | Dongxian Zhang, Ma Cl, Lihua Li, Yan Qw, Shi Zj, Yang Yu, Genmeng Yang, Li L, Zhao Yn, Zhang Zb, Hong Shijun, Xiaofeng Zeng |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Apoptosis Pharmacology Toxicology CREB Neuroprotection Methamphetamine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucosides medicine Cyclic AMP Animals Cyclic adenosine monophosphate Gastrodin Protein kinase A Cyclic AMP Response Element-Binding Protein Benzyl Alcohols Cells Cultured Brain-derived neurotrophic factor Neurons biology Brain-Derived Neurotrophic Factor Neurotoxicity Motor Cortex General Medicine medicine.disease Cyclic AMP-Dependent Protein Kinases 030104 developmental biology Neuroprotective Agents chemistry biology.protein Female Neurotoxicity Syndromes 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Humanexperimental toxicology. 39(8) |
| ISSN: | 1477-0903 |
| Popis: | Objective: Methamphetamine (MA) abuse induces neurotoxicity and causes neuronal cell apoptosis. Gastrodin is a traditional Chinese herbal medicine used for the treatment of nerve injuries, spinal cord injuries, and some central nervous system diseases as well. The present study investigated the neuroprotective effects of gastrodin against MA-induced neurotoxicity in neuronal cells and its potential protective mechanism. Methods: The primary cortex neuronal culture was divided into four groups (control group, MA group, MA + gastrodin group, and MA + gastrodin + small interfering RNA group). The neurotoxicity of MA was assessed by detecting apoptotic cells by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay and cell viability by cell counting kit 8 (CCK-8) method, the Tuj1-positive cells and the average axonal length were detected by immunofluorescence, and the expressions of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding (CREB), and brain-derived neurotrophic factor (BDNF) proteins were detected by Western blot. Results: The results of CCK-8 assay showed that 0.5 mM MA was an optimal concentration that induced neurotoxicity ( p < 0.01). Pretreatment with 25 mg/L gastrodin exerted maximum protective effects on neuronal cells. The expression levels of cAMP, PKA, phosphorylated PKA, CREB, phosphorylated CREB, and BDNF proteins were decreased in the MA group, and pretreatment with gastrodin upregulated the expression levels of these proteins ( p < 0.01). The expressions of PKA and CREB proteins showed no significant changes in the control group, MA group, and gastrodin group. Compared the MA + gastrodin + small interfering RNA group with MA + gastrodin group, the Tuj1-positive cells and the average axonal length were decreased significantly, while the number of apoptotic cells was increased ( p < 0.05). Conclusion: Gastrodin has neuroprotective effects against MA-induced neurotoxicity, which exerts neuroprotective effects via regulation of cAMP/PKA/CREB signaling pathway and upregulates the expression of BDNF. |
| Databáze: | OpenAIRE |
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