Carnosine Improves Cognitive Impairment Through Promoting SIRT6 Expression and Inhibiting Endoplasmic Reticulum Stress in a Diabetic Encephalopathy Model.

Abstract

Diabetic encephalopathy (DE) is one of complications of diabetes mellitus. Carnosine is a dipeptide composed of β-alanine and l-histidine. Study has shown that carnosine could ameliorate cognitive impairment in animal model with diabetes mellitus. However, the mechanism remains unclear. An animal model of type 2 diabetes (db/db mice) was used in this study. The animals were treated with 0.9% saline or carnosine (100 mg/kg) for 8 weeks. Morris water maze was tested after drug administration. Oxidative stress-related factors malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and pro-inflammatory factors inducible nitric oxide synthase (iNOS) were measured. Synapse-related protein postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF) were detected by western blot. Besides, the expressions of sirtuin 6 (SIRT6), binding immunoglobulin protein (BIP), protein kinase R-like endoplasmic reticulum kinase (PERK), phospho-protein kinase R-like endoplasmic reticulum kinase (P-PERK), inositol-requiring enzyme-1α (IRE1α), phospho-inositol-requiring enzyme-1α (P-IRE1α), activating transcription factor 6 (ATF6), and C/EBP-homologous protein (CHOP) in the hippocampus of the brain were detected. The results showed that treatment with carnosine ameliorated cognitive impairment in db/db mice. Carnosine reduced neuronal oxidative stress damage and iNOS expression in db/db mice. Meanwhile, carnosine relieved neurodegeneration in the hippocampus of db/db mice. Furthermore, carnosine promoted the expression of SIRT6 and reduced the expressions of endoplasmic reticulum (ER)-related factors (BIP, P-PERK, P-IRE1α, ATF6, and CHOP). In conclusion, these data suggested that the protective effect of carnosine against DE might be related to SIRT6/ER stress pathway.

• Authors: Dong Peng, Qing Xia, Li Guan, Hong-Ying Li, Li-Jun Qiao, Yun-Bo Chen, Ye-Feng Cai, Qi Wang, Shi-Jie Zhang
• Journal: Rejuvenation research (Rejuvenation Res) Vol. 25 Issue 2 Pg. 79-88 (Apr 2022) ISSN: 1557-8577 [Electronic] United States
• PMID: 35302398 (Publication Type: Journal Article)

Chemical References

• Carnosine
• Sirt6 protein, mouse
• Protein Serine-Threonine Kinases
• Endoribonucleases
• Sirtuins

Topics

• Animals
• Apoptosis
• Brain Diseases
• Carnosine (pharmacology, therapeutic use)
• Cognitive Dysfunction (drug therapy)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Endoplasmic Reticulum Stress
• Endoribonucleases (genetics)
• Mice
• Protein Serine-Threonine Kinases
• Sirtuins (genetics)