Parkinson's disease (PD) is an age-associated neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Activation of 5′-adenosine monophosphate-activated protein kinase (AMPK) has been suggested to be associated with PD pathogenesis. The aim of the present study was to investigate the effects of the aberrant expression of microRNA-185 (miR-185) in PD. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced in vitro model of PD was generated using the human SH-SY5Y dopaminergic neuroblastoma cell line, in order to examine the potential molecular mechanisms underlying the roles of miR-185 in PD. miR-185 expression was assessed in MPTP-treated SH-SY5Y cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, MPTP-treated SH-SY5Y cells were transfected with a miR-185 mimic or scramble miRNA, and flow cytometry was used to evaluate the level of cellular apoptosis. The expression of autophagy markers, including Beclin 1, microtubule-associated protein light chain 3 (LC3) I and LC3II, as well as key molecules involved in the AMPK/mechanistic target of rapamycin (mTOR) signaling pathway, such as phosphorylated (p)-AMPK and p-mTOR, was examined using RT-qPCR and western blot analyses. In addition, SH-SY5Y cells were treated with the AMPK inhibitor, Compound C, and its effects on cellular apoptosis were assessed. The results demonstrated that miR-185 was significantly downregulated in SH-SY5Y cells treated with MPTP at concentrations of >100 µM when compared with untreated controls. Following transfection with a miR-185 mimic, miR-185 expression in SH-SY5Y cells was significantly increased when compared with blank control cells. Notably, miR-185 overexpression was revealed to significantly reduce the MPTP-induced increase in cellular apoptosis. In addition, the expression levels of Beclin 1, LC3I/II, p-AMPK and p-mTOR were significantly upregulated in MPTP-treated SH-SY5Y cells; whereas miR-185 overexpression significantly downregulated the expression of these factors. Furthermore, miR-185 overexpression significantly suppressed apoptosis of SH-SY5Y cells treated with MPTP plus Compound C when compared with the Compound C group. In conclusion, the results of the present study suggest that overexpression of miR-185 may inhibit autophagy and apoptosis of dopaminergic cells in PD potentially via regulation of the AMPK/mTOR signaling pathway. Therefore, AMPK/mTOR-mediated autophagy and apoptotic signaling pathways may be potential novel therapeutic targets for the development of alternative strategies for the treatment of patients with PD.
BackgroundPrevious studies demonstrated that early blindness is associated with abnormal intrinsic functional connectivity (FC) between the primary visual cortex (V1) and other sensory areas. However, the V1 pattern of spontaneous neural activity occurring in late blindness (LB) remains unknown. The purpose of this study was to investigate the intrinsic FC patterns of V1 in LB.Materials and methodsThirty LB individuals (18 males and 12 females; mean age: 38.76±14.43 years) and 30 sighted controls (SCs) individuals (18 males and 12 females; mean age: 38.67±13.85 years) closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Region of interest analysis was performed to extract the correlation coefficient matrix among each pair of Brodmann area (BA) 17 and FC between V1 and vision-related subcortical nuclei.ResultsCompared with SCs, LB individuals showed a decreased FC between the left V1 and the bilateral cuneus (CUN)/lingual gyrus (LGG)/calcarine (CAL) (BA 18/19/30) and left precentral gyrus (PreCG) and the postcentral gyrus (PostCG) (BA 2/3/4). Also, LB individuals showed a decreased FC between the right V1 and the bilateral CUN/LGG/CAL (BA 18/19/30) and the left PreCG and PostCG (BA 2/3/4/6) (voxel-level: P<0.01, cluster-level: P<0.05). Meanwhile, LB individuals showed a decreased FC between the left V1 and the right V1 and increased FC between the left V1 and the right superior colliculus, the right V1, and the left hippocampus (P<0.05). Moreover, a positive correlation was observed between the onset age of blindness and FC values in V1 to CUN/LGG/CAL in LB.ConclusionOur results highlighted that LB induces a decreased FC between V1 and higher visual areas, motor cortices, and somatosensory cortices at rest. This might indicate that LB humans could present with impaired top-down modulations, visual imagery, and vision-motor function.
Chitosan and PEG-based self-healable in situ hydrogel developed as a long-term MRI reporter.
Human immunodeficiency virus (HIV) infection significantly affect neurodevelopmental and behavioral outcomes. We investigated whether alterations of gray matter organization and structural covariance networks with vertical HIV infection adolescents exist, by using the GAT toolbox. MRI data were analysed from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control participants. The gray matter volume (GMV) was calculated, and structural brain networks were reconstructed from gray matter co-variance. Gray matter losses were pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in frontal, temporal, basal ganglia, cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased in number and tended to shift to sensorimotor and temporal areas. In the HIV-infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to lower Mini-Mental State Examination scores; the CD4 counts were positively related to the GMVs in ACC and sensorimotor areas. These findings suggest that focally reduced gray matter, disrupted nodal profiles of structural wirings, and a shift in hub distribution may represent neuroanatomical biomarkers of HIV infection on the developing brain.
Combined with SWE, US yielded higher specificity for nodules of 10 mm and smaller and higher sensitivity for nodules larger than 10 mm.
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