Astrocytes and neurons in locus coeruleus mediate restraint water immersion stress-induced gastric mucosal damage through the ERK1/2 signaling pathway

Abstract

Restraint water-immersion stress (RWIS) is considered to be a compound stress model that includes psychological and physical stimulation and may cause gastric mucosal damage. Studies have shown that locus coeruleus (LC) is involved in the gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported. Here, we investigated the expression of glial fibrillary acidic protein (GFAP), c-Fos, and phosphorylation extracellular signal regulated kinase 1/2 (p-ERK1/2) in the LC after RWIS using immunocytochemical staining and western blotting in order to explore whether the ERK1/2 signaling pathway interacts with the neuron-astrocyte network in the LC during RWIS and whether it is involved in causing RWIS-induced gastric mucosal damage. Expression of c-Fos, GFAP, and p-ERK1/2 increased significantly following RWIS and peaked at 3 h after RWIS. After intracerebroventricular injection of c-Fos antisense oligodeoxynucleotides (ASO) and astrocytic toxin L-a-aminoadipate (L-AA), the gastric mucosal damage and the activation of neurons and astrocytes in the LC significantly decreased. Intracerebroventricular injection of ERK1/2 signaling pathway inhibitor PD98059 suppressed gastric mucosal damage as well as the RWIS-induced activation of neurons and astrocytes in the LC. Activation of LC neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may play a critical role in RWIS-induced gastric mucosa damage.