Neuroscience
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Review
The biology, pathological roles of exosomes and their clinical application in Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease with a high global incidence and places a great burden on the patient, their family and society. Early diagnosis of PD is the key to hindering the progression process and may enable treatment to partially reverse the disease course. Exosomes are lipid bilayers with a diameter of 40-160 nm (average ∼100 nm), show a cup-shaped structure in transmission electron microscopy (TEM) images, and contain different types of nucleic acids and proteins. ⋯ Of course, exosomes also have great potential as drug delivery systems due to their low toxicity, lipid solubility and immunological inertness. However, there is still a lack of standardized, efficient, and ultrasensitive methods for the isolation of exosomes, hindering the development of effective biomarkers. Therefore, this review describes the biological characteristics of exosomes, exosome extraction methods, and the pathological role, diagnostic/therapeutic value of exosomes in PD.
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Selective impairment in recognizing facial expressions of disgust was reported in patients with focal dystonia several years ago, but the basic neural mechanisms remain largely unexplored. Therefore, we investigated whether dysfunction of the brain network involved in disgust recognition processing was related to this selective impairment in blepharospasm. Facial emotion recognition evaluations and resting-state functional magnetic resonance imaging were performed in 33 blepharospasm patients and 33 healthy controls (HCs). ⋯ We identified decreased functional activity in these regions, as indicated by a lower amplitude of low-frequency fluctuation in the left MOG, fractional amplitude of low-frequency fluctuation in the right FG, and regional homogeneity in the right FG and left MOG in blepharospasm patients versus HCs. Our results suggest that dysfunctions of the disgust processing network exist in blepharospasm. A deficit in disgust emotion recognition may be attributed to disturbances in the early perception of visual disgust stimuli in blepharospasm patients.
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Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by the progressive cognitive decline. Among the various clinical symptoms, neuropsychiatric symptoms (NPS) commonly occur during the course of AD. Previous researches have demonstrated a strong association between NPS and severity of AD, while the research methods are not sufficiently intuitive. ⋯ According to the experimental results, our model achieves an accuracy of 0.91 and an area under the curve of 0.97 in the task of classifying AD and cognitively normal individuals. SHapley Additive exPlanations are used to visually exhibit the contribution of specific NPS in the proposed model. Among all behavioral symptoms, apathy plays a particularly important role in the diagnosis of AD, which can be considered a valuable factor in further studies, as well as clinical trials.
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Fluvastatin (FLV), the first synthetically derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is a potent inhibitor of cholesterol biosynthesis. While its primary mechanism of action is to reduce cholesterol levels, there is some evidence suggesting that it may also have effects on K+ channels. However, the overall effects of fluvastatin on ionic currents are not yet well understood. ⋯ Our study presents compelling evidence indicating that FLV has the potential to impact both the amplitude and gating of the ion channels IK(erg) and Ih. We also provide credible evidence suggesting that this drug has the potential to modify the properties of action potentials and the afterhyperpolarization current in electrically excitable cells. However, the assumption that these findings translate to similar in-vivo results remains unclear.
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Spontaneous subarachnoid hemorrhage (SAH) is an acute neurologic emergency with poor outcomes, and mitochondrial dysfunction is known as one of the key pathological mechanisms underlying the SAH-induced early brain injury (EBI). 1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate (T817MA) is a newly synthesized neurotrophic compound that has been demonstrated to exert protective effects against brain injury. Here, we investigated the effect of T817MA in neuronal injury following experimental SAH both in vitro and in vivo. Primary cultured cortical neurons were treated with oxyhemoglobin (OxyHb) to mimic SAH in vitro, and T817MA at concentrations higher than 0.1 μM reduced OxyHb-induced neuronal injury. ⋯ Furthermore, treatment with T817MA in vivo significantly reduced brain damage and preserved neurological function in rats. The decreased expression of Fis-1 and Drp-1, as well as the increased expression of Arc and Sirt1 were also observed in vivo. Taken together, these data indicate that the neuroprotective agent T817MA protects against SAH-induced brain injury via Sirt1- and Arc-mediated regulation of mitochondrial dynamics.