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Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron.
Hum Exp Toxicol. 2020 Aug; 39(8):1118-1129.HE

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.

Authors+Show Affiliations

The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China. Department of Laboratory Animal, School of Basic Medicine, Kunming Medical University, Kunming, People's Republic of China.School of International Education, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.School of Basic Medical Sciences, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.The School of Forensic Medicine, Kunming Medical University, Kunming, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32162539

Citation

Ma, C-L, et al. "Neuroprotective Effect of Gastrodin in Methamphetamine-induced Apoptosis Through Regulating cAMP/PKA/CREB Pathway in Cortical Neuron." Human & Experimental Toxicology, vol. 39, no. 8, 2020, pp. 1118-1129.
Ma CL, Li L, Yang GM, et al. Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron. Hum Exp Toxicol. 2020;39(8):1118-1129.
Ma, C. L., Li, L., Yang, G. M., Zhang, Z. B., Zhao, Y. N., Zeng, X. F., Zhang, D. X., Yu, Y., Shi, Z. J., Yan, Q. W., Li, L. H., & Hong, S. J. (2020). Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron. Human & Experimental Toxicology, 39(8), 1118-1129. https://doi.org/10.1177/0960327120911438
Ma CL, et al. Neuroprotective Effect of Gastrodin in Methamphetamine-induced Apoptosis Through Regulating cAMP/PKA/CREB Pathway in Cortical Neuron. Hum Exp Toxicol. 2020;39(8):1118-1129. PubMed PMID: 32162539.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron. AU - Ma,C-L, AU - Li,L, AU - Yang,G-M, AU - Zhang,Z-B, AU - Zhao,Y-N, AU - Zeng,X-F, AU - Zhang,D-X, AU - Yu,Y, AU - Shi,Z-J, AU - Yan,Q-W, AU - Li,L-H, AU - Hong,S-J, Y1 - 2020/03/12/ PY - 2020/3/13/pubmed PY - 2021/2/20/medline PY - 2020/3/13/entrez KW - Methamphetamine KW - brain-derived neurotrophic factor KW - cAMP-response element-binding protein KW - cyclic adenosine monophosphate KW - gastrodin KW - protein kinase A SP - 1118 EP - 1129 JF - Human & experimental toxicology JO - Hum Exp Toxicol VL - 39 IS - 8 N2 - 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. SN - 1477-0903 UR - https://www.unboundmedicine.com/medline/citation/32162539/Neuroprotective_effect_of_gastrodin_in_methamphetamine_induced_apoptosis_through_regulating_cAMP/PKA/CREB_pathway_in_cortical_neuron_ L2 - https://journals.sagepub.com/doi/10.1177/0960327120911438?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -