Hippocampal proteins discovery of diabetes-induced central neuropathy based on proteomics.

OBJECTIVES: Growing evidence suggests that diabetes can cause multifactorial damage to the central nervous system (CNS) and may lead to dementia. However, the underlying mechanism of diabetes-induced central neuropathy remains sparse. In recent years, proteomics has provided better methods and means in analyzing the molecular mechanisms of disease. We applied proteomics to investigate the changes of hippocampal proteins in diabetic rats, with a view to discover the biomarkers of diabetes-induced central neuropathy and elucidated the potential biological relationships. METHODS: Male Wistar rats were randomly divided into the control group and model group. The model group rats were injected intraperitoneally with streptozotocin. Morris water maze test was performed to evaluate the learning and memory of rats, and the hippocampus was taken out. Proteomics were adopted to investigate the changes of differentially expressed proteins. RESULTS: Compared with the control group, the escape latency of the diabetic rats was significantly increased (P < 0.01, P < 0.05). It was presented that four differentially expressed proteins might be the potential biomarkers of diabetes-induced central neuropathy: septin 5, GRB2 related binding protein 2 (GAB2), casein kinase 1ε (CK1ε), aquaporin 4 (AQP4). These differentially expressed proteins were mainly involved in the following signaling pathways: apoptosis, glycine/serine/threonine metabolic and GTPase signaling pathway. CONCLUSIONS: These findings provided reference insights into the underlying molecular pathogenesis of diabetes-induced CNS neuropathy.

Cerebrospinal Fluid Amino Acid Metabolite Signatures of Diabetic Cognitive Dysfunction Based on Targeted Mass Spectrometry.

BACKGROUND: Diabetic cognitive dysfunction (DCD) is one of severe diabetic complications and might develop to irreversible dementia. Early diagnosis and detection of DCD is significant for prevention and treatment. OBJECTIVE: The main objective of this study was to investigate the amino acid profiles of rat with DCD in the cerebrospinal fluid (CSF) to distinguish the early specific biomarkers. METHODS: In total, rats were assigned into control and model groups. Model was induced by intraperitoneal injection of streptozotocin. The Morris water maze (MWM) method was used to evaluate learning and memory in rats on the 13th week after the model established. CSF samples were collected via cisterna magna puncture at the 0th, 5th, 9th, and 13th week, and amino acids profiling of CSF samples were performed via ultra performance liquid chromatography multiple reaction monitoring mass spectrometry (UPLC-MRM-MS). The amino acid profile was processed through multivariate analysis to identify potential biomarkers, and the related metabolic pathways were analyzed by MetaboAnalyst 5.0. RESULTS: Compared to the control group, the escape latency of the MWM was significantly prolonged in model group rats (p < 0.05). Different amino acid profiles were obtained between two groups. L-Alanine, L-Glutamine, L-Lysine, L-Serine, and L-Threonine were identified as potential biomarkers for DCD. These biomarkers are principally involved in glycine, serine, and threonine metabolism, aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and glyoxylate and dicarboxylate metabolism. CONCLUSION: There are amino acid biomarkers in the CSF of rat with DCD. The mechanism of DCD is related to those pathways, which provide help for the early diagnosis and treatment and mechanism research.

Spatiotemporally Controllable MicroRNA Imaging in Living Cells via a Near-Infrared Light-Activated Nanoprobe.

In situ spatiotemporal microRNA (miRNA) imaging in mammal cells plays an essential role in illustrating its structures and biological functions. Herein, we proposed a near-infrared (NIR) light-activated nanoprobe for high-sensitive in situ controllable miRNA imaging in living cells. The NIR-activated nanoprobe employed an upconversion nanoparticle that acted as a NIR-to-UV transducer to trigger the following photocleavage toward a dumbbell DNA probe tethered on the surface of the nanoparticle. The structure change of the dumbbell probe then induced a catalytic hairpin assembly of target miRNAs, by which in situ readout of the amplified fluorescence signal was enabled. Additionally, both intracellular miRNA imaging and accurate quantification in live cells were realized without damaging the cell membranes. Compared with conventional in situ strategies, the proposed approach remarkedly increases imaging efficiency by eliminating those unfavored intercellular molecular imaging backgrounds. We assured that the proposed NIR-activated miRNA sensing strategy will add to the advancement for bioanalysis in living systems, which is of crucial importance in the diagnosis of various human diseases, especially cancers.