Neuroscience
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Review
The potential role of AMPA receptor trafficking in autism and other neurodevelopmental conditions.
Autism Spectrum Disorder (ASD) is a multifaceted condition associated with difficulties in social interaction and communication. It also shares several comorbidities with other neurodevelopmental conditions. Intensive research examining the molecular basis and characteristics of ASD has revealed an association with a large number and variety of low-penetrance genes. ⋯ Despite the high genetic heterogeneity in ASD, surface trafficking of the α-amino-3-hydroxy-5-Methyl-4-isoxazolepropionate (AMPA) receptor is a vulnerable pathway in ASD. In this review, we discuss autism-related alterations in the trafficking of AMPA receptors, whose surface density and composition at the post-synapse determine the strength of the excitatory connection between neurons. We highlight genes associated with neurodevelopmental conditions that share the autism comorbidity, including Fragile X syndrome, Rett Syndrome, and Tuberous Sclerosis, as well as the autism-risk genes NLGNs, IQSEC2, DOCK4, and STXBP5, all of which are involved in regulating AMPAR trafficking to the post-synaptic surface.
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In recent decades, our understanding of the molecular changes involved in neurodegenerative diseases has been transformed. Single-cell RNA sequencing and single-nucleus RNA sequencing technologies have been applied to provide cellular and molecular details of the brain at the single-cell level. This has expanded our knowledge of the central nervous system and provided insights into the molecular vulnerability of brain cell types and underlying mechanisms in neurodegenerative diseases. In this review, we highlight the recent advances and findings related to neurodegenerative diseases using these cutting-edge technologies.
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Randomized Controlled Trial
Effect of High-definition Transcranial Direct Current Stimulation on Conditioned Pain Modulation in Healthy Adults: A Crossover Randomized Controlled Trial.
The disorder of the conditioned pain modulation (CPM) system is one of the main causes of pain perception in individuals. High-definition transcranial direct current stimulation (HD-tDCS) targeting specific brain areas was indicated to have an analgesic effect possibly by activating the endogenous pain inhibition pathway evident in CPM. However, discrepancies were found in previous limited studies of varied homogeneity and quality. ⋯ The changes of CPM were positively correlated with the total physical activity volume. In conclusion, our findings provide evidence support to the effectiveness of HD-tDCS on endogenous pain modulation among healthy adults. Further studies are required to explore the analgesic effect of tDCS among patients with chronic pain, thereby facilitating optimal chronic pain management.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) binds to PACAP-specific (PAC1) receptors in multiple hypothalamic areas, especially those regulating energy balance. PACAP neurons in the ventromedial nucleus (VMN) exert anorexigenic effects within the homeostatic energy balance circuitry. Since PACAP can also reduce the consumption of palatable food, we tested the hypothesis that VMN PACAP neurons project to the ventral tegmental area (VTA) to inhibit A10 dopamine neurons via PAC1 receptors and KATP channels, and thereby suppress binge-like consumption. ⋯ This response was again completely blocked by tolbutamide and PACAP6-38, and associated with a hyperpolarization and decrease in firing. These findings demonstrate that PACAP activates PAC1 receptors and KATP channels to inhibit A10 dopamine neurons and sex-dependently suppress binge-like consumption. Accordingly, they advance our understanding of how PACAP regulates energy homeostasis via the hedonic energy balance circuitry.
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Drug-resistant temporal lobe epilepsy (TLE) is a potential candidate for surgery; however, nearly one-third subjects had a poor surgical prognosis. We studied the underlying neuromechanism related to the surgical prognosis using graph theory based on metabolic brain network. Sixty-four unilateral TLE subjects with preoperative 18F-fluorodeoxyglucose (FDG) PET scanning were retrospectively enrolled and divided into Ia (Engel class Ia, n = 32) and non-Ia (Engel class Ib-IV, n = 32) groups according to more than 3-year follow-up after unilateral anterior temporal lobectomy (ATL). ⋯ Graph theoretical analysis revealed that non-Ia group showed increased small-worldness (35%