Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice
Envoyer une demande de publication
close

Demande de publication

Merci pour votre intérêt pour nos produits et votre demande concernant cette publication, qui vous sera envoyée si le chercheur et le journal l'autorisent. Notre équipe commerciale vous contactera rapidement.



- Catégories : Diabète, Insuline & Glucose , Publications - ID: 1505

Authors
X Chen, Y Le, SQ Tang et al


Lab
Department of Anesthesiology, The First PeopleÕs Hospital of Foshan, Foshan, Guangdong, China

Journal
Oxidative Medicine and Cellular Longevity

Abstract
Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods. Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results. The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1beta, TNF-alpha, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1beta, TNF-alpha, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions. Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.

BIOSEB Instruments Used:
Electronic Von Frey 5 with embedded camera (BIO-EVF5),Electronic Von Frey 4 (BIO-EVF4)

Partager ce contenu