Neuroprotective effect of gastrodin in methamphetamine-induced apoptosis through regulating cAMP/PKA/CREB pathway in cortical neuron

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.

Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function

“…Conversely, Sigmar1 genetic ablation attenuates CREB expression and pCREBSer133 expression. Our findings are agreement with studies that demonstrated that chronic METH treatment in rats (4 mg/kg, IP, 2 weeks) resulted in decreased CREB/pCREB immunostaining in the neuronal nuclei of striatum 60 and decreased pCREB expression in METH-treated cultured primary cortical neurons 61 . Similarly, both acute and repeated METH exposure (5 mg/kg, IP) suppresses the striatal expression of CREB mRNA 62 .…”

Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats

“…The insufficient expression of ADCY by the D-gal induction can lead the reduction of the cAMP expression. The attenuated expression of the cAMP may further lead to the protein kinase (PKA) inactivation, following which to inhibit the expression of phosphorylated cAMP response element binding protein (CREB) [ 65 ]. The CREB is a molecular switch that is the core component of long-term memory.…”

Cannabidiol Attenuates Methamphetamine-Induced Cardiac Inflammatory Response and Necrosis through The PKA/CREB Signaling Pathway

“…PKA, p-PKA, CREB, and p-CREB are highly expressed in different brain regions of MA-induced conditioned place preference (CPP) rats and in SH-SY5Y cells, but can be inhibited by gastrodin (Yang et al, 2020b). The cAMP/PKA/CREB pathway is also involved in the apoptosis of cortical neurons induced by MA, but can be regulated by the neuroprotective effects of gastrodin (Ma et al, 2020). In this study, the expression levels of PKA, p-PKA, CREB, and p-CREB decreased following CBD pretreatment, indicating that CBD may attenuate myocardial in ammation and cardiac pathology by mediating the PKA/CREB signaling pathway.…”