Ghrelin ameliorates nerve growth factor Dysmetabolism and inflammation in STZ-induced diabetic rats

• Published in: Metabolic brain disease Vol. 32; no. 3; pp. 903 - 912
• Main Authors: Zhao, Yuxing, Shen, Zhaoxing, Zhang, Dongling, Luo, Huiqiong, Chen, Jinliang, Sun, Yue, Xiao, Qian
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2017; Springer Nature B.V
• Subjects: Activation; Amino acids; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood Glucose - drug effects; Blood Glucose - metabolism; Brain; Cognitive ability; Degeneration; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Encephalopathy; Ghrelin; Ghrelin - administration & dosage; Growth factors; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Injections, Intraventricular; Interleukin 6; Kinases; Male; Matrilysin; Matrix metalloproteinase; Metabolic Diseases; Metalloproteinase; Nerve growth factor; Nerve Growth Factor - metabolism; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neurology; Neuromodulation; Neurosciences; Oncology; Original Article; Protein kinase; Rats; Rats, Sprague-Dawley; Rodents; Streptozocin; Synaptic density; Synaptophysin; Nerve growth factor; Inflammation; Diabetes; Neurodegeneration; Ghrelin
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-017-0001-9

Diabetic encephalopathy is characterized by cognitive impairment and neuroinflammation, deficient neurotrophic support, and neuronal and synaptic loss. Ghrelin, a 28 amino acid peptide, is associated with neuromodulation and cognitive improvement, which has been considered as a potential protective agent for several neurodegenerative diseases. Here we sought to investigate the role of ghrelin in preventing diabetic-related neuropathology. We found that ghrelin attenuated astrocytic activation and reduced levels of interleukin-6 and tumor necrosis factor-α in streptozotocin-induced diabetic rats. In addition, ghrelin inhibited p38 mitogen-associated protein kinase activation. The upregulation of nerve growth factor (NGF) precursor and matrix metalloproteinase (MMP)-9 and downregulation of mature NGF and MMP-7 in the diabetic brain were reversed by ghrelin. Treatment with ghrelin elevated synaptophysin expression and synaptic density in diabetic rats. Taken together, our results demonstrate that ghrelin ameliorates diabetes-related neurodegeneration by preventing NGF dysmetabolism and synaptic degeneration through regulating MMP levels as well as inhibiting neuroinflammation.