Neuroscience
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Sensory difficulties represent a crucial issue in the life of autistic individuals. The diagnostic and statistical manual of mental disorders describes both hyper- and hypo-responsiveness to sensory stimulation as a criterion for the diagnosis autism spectrum disorders (ASD). Among the sensory domain affected in ASD, altered responses to tactile stimulation represent the most commonly reported sensory deficits. ⋯ Here we investigated the gene expression deregulation in the trigeminal ganglion (which directly receives tactile information from whiskers) in two genetic models of syndromic autism (Shank3b and Cntnap2 mutant mice) at both adult and juvenile ages. We found several neuronal and non-neuronal markers involved in inhibitory, excitatory, neuroinflammatory and sensory neurotransmission to be differentially regulated within the trigeminal ganglia of both adult and juvenile Shank3b and Cntnap2 mutant mice. These results may help in disentangling the multifaced complexity of sensory abnormalities in autism and open avenues for the development of peripherally targeted treatments for tactile sensory deficits exhibited in ASD.
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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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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.