ABSTRACT
Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment.
Subject(s)
Choroid Plexus , Cognitive Dysfunction , Diffusion Tensor Imaging , Glymphatic System , White Matter , Humans , Male , Female , Choroid Plexus/diagnostic imaging , Choroid Plexus/pathology , Choroid Plexus/physiopathology , White Matter/diagnostic imaging , White Matter/pathology , Aged , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Glymphatic System/physiopathology , Middle Aged , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/pathology , Neuropsychological Tests , Magnetic Resonance Imaging/methods , Processing SpeedABSTRACT
BACKGROUND: A number of dysregulated miRNAs have been identified and are proposed to have significant roles in the pathogenesis of type 2 diabetes mellitus or renal pathology. Alpinia oxyphylla has shown significant anti-inflammatory properties and play an anti-diabetes role. The objective of this study was to detect the alteration of miRNAs underlying the anti-diabetes effects of A. oxyphylla extract (AOE) in a type II diabetic animal model (C57BIKsj db-/db-). RESULTS: Treatment with AOE for 8 weeks led to lower concentrations of blood glucose, urine albumin, and urine creatinine. 17 and 13 miRNAs were statistically identified as differentially regulated in the DB/DB and db-/db- AOE mice, respectively, compared to the untreated db-/db- mice. Of these, 7 miRNAs were identified in both comparison groups, and these 7 miRNAs were verified by quantitative real-time PCR. Functional bioinformatics showed that the putative target genes of 7 miRNAs were associated with several diabetes effects and signaling pathways. CONCLUSIONS: These founding suggest that the potential of AOE as a medicinal anti-diabetes treatment through changes in the expressions of specific miRNAs. The results provide a useful resource for future investigation of the role of AOE-regulated miRNAs in diabetes mellitus.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Kidney/drug effects , MicroRNAs/drug effects , Plant Extracts/pharmacology , Albuminuria , Alpinia , Animals , Blood Glucose/analysis , Creatinine/blood , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Gene Expression Regulation , Kidney/metabolism , Male , Mice, Inbred C57BL , MicroRNAs/metabolism , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Sequence Analysis, RNA , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: A number of dysregulated miRNAs have been identified and are proposed to have significant roles in the pathogenesis of type 2 diabetes mellitus or renal pathology. Alpinia oxyphylla has shown significant anti-inflammatory properties and play an anti-diabetes role. The objective of this study was to detect the alteration of miRNAs underlying the anti-diabetes effects of A. oxyphylla extract (AOE) in a type II diabetic animal model (C57BIKsj db-/db-). RESULTS: Treatment with AOE for 8 weeks led to lower concentrations of blood glucose, urine albumin, and urine creatinine. 17 and 13 miRNAs were statistically identified as differentially regulated in the DB/DB and db-/db- AOE mice, respectively, compared to the untreated db-/db- mice. Of these, 7 miRNAs were identified in both comparison groups, and these 7 miRNAs were verified by quantitative real-time PCR. Functional bioinformatics showed that the putative target genes of 7 miRNAs were associated with several diabetes effects and signaling pathways. CONCLUSIONS: These founding suggest that the potential of AOE as a medicinal anti-diabetes treatment through changes in the expressions of specific miRNAs. The results provide a useful resource for future investigation of the role of AOE-regulated miRNAs in diabetes mellitus.
