Activation of CaMKII and GluR1 by the PSD-95-GluN2B Coupling-Dependent Phosphorylation of GluN2B in the Spinal Cord in a Rat Model of Type-2 Diabetic Neuropathic Pain

Autor: Ya Bing Zhu, Jun Wu Wang, Yu Jing Shen, Hong Cao, Jia Li Chen, Xiu Ying Ye, Jia Hui Lu, Gai Li Jia, Jun Li, Mao Biao Zhang, Ci Shan Xie, Yuan Xiang Tao
Rok vydání: 2019
Předmět:
Male
medicine.medical_specialty
Receptors
N-Methyl-D-Aspartate
Pathology and Forensic Medicine
Rats
Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Diabetic Neuropathies
Postsynaptic potential
Ca2+/calmodulin-dependent protein kinase
Diabetes mellitus
Internal medicine
mental disorders
medicine
Animals
Receptors
AMPA
Phosphorylation
030304 developmental biology
0303 health sciences
Chemistry
musculoskeletal
neural
and ocular physiology
Antagonist
General Medicine
medicine.disease
Spinal cord
Rats
Coupling (electronics)
Disease Models
Animal
medicine.anatomical_structure
Endocrinology
nervous system
Neurology
Diabetes Mellitus
Type 2
Spinal Cord
Neuropathic pain
Neurology (clinical)
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Disks Large Homolog 4 Protein
psychological phenomena and processes
030217 neurology & neurosurgery
Zdroj: Journal of neuropathology and experimental neurology. 79(7)
ISSN: 1554-6578
Popis: The mechanisms underlying type-2 diabetic neuropathic pain (DNP) are unclear. This study investigates the coupling of postsynaptic density-95 (PSD-95) to N-methyl-D-aspartate receptor subunit 2B (GluN2B), and the subsequent phosphorylation of GluN2B (Tyr1472-GluN2B) in the spinal cord in a rat model of type-2 DNP. Expression levels of PSD-95, Tyr1472-GluN2B, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and its phosphorylated counterpart (Thr286-CaMKII), and α-amino-3-hydroxy-5-methyl-4-soxazole propionic acid receptor subtype 1 (GluR1) and its phosphorylated counterpart (Ser831-GluR1) were significantly increased versus controls in the spinal cord of type-2 DNP rats whereas the expression of total spinal GluN2B did not change. The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the interaction between PSD-95 and GluN2B) induced an antihyperalgesic effect and blocked the increased expression of Tyr1472-GluN2B, CaMKII, GluR1, Thr286-CaMKII, and Ser831-GluR1 in the spinal cords; the increase in spinal cord PSD-95 was not affected. These findings indicate that the PSD-95-GluN2B interaction may increase phosphorylation of GluN2B, and subsequently induce the expression of phosphorylation of CaMKII and GluR1 in the spinal cord of type-2 DNP rats. Targeting the interaction of PSD-95 with GluN2B may provide a new therapeutic strategy for type-2 DNP.
Databáze: OpenAIRE
Externí odkaz: