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Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron
- Source :
- Humanexperimental toxicology. 39(8)
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14770903
- Volume :
- 39
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Humanexperimental toxicology
- Accession number :
- edsair.doi.dedup.....c73e76f14ee74ad30c678da05c4aa3ea