Here at ADInstruments, we're lucky to be a part of a large and thriving research community. Join us in celebrating some of the incredible work published by that community in November 2024.
Chemogenetics with PSAM4-GlyR decreases excitability and epileptiform activity in epileptic hippocampus
Published in Gene Therapy
Gonzalez-Ramos et al., are exploring the use of chemogenetic therapy as a potential treatment for drug-resistant epilepsy. Their article investigates the efficacy of PSAM4-GlyR, a synthetic chloride-permeable ion channel, activated by the ligand uPSEM817. In vitro experiments demonstrated that activation of PSAM4-GlyR reduced neuronal excitability by shunting depolarizing currents, leading to fewer action potentials. Organotypic slices of the hippocampus also showed a decrease in epileptiform activity, including reduced burst frequency and peak amplitudes. However, in vivo administration of uPSEM817 in a mouse model of temporal lobe epilepsy did not significantly reduce electrographic seizures, though there was a trend toward reduced seizures.
Read more: https://pubmed.ncbi.nlm.nih.gov/39455855/
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Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation
Published in Nature Neuroscience
Are dorsal root ganglion neurons, a critical component of somatosensory function, the same across species? Using a novel approach that combines laser capture microdissection and deep single-soma RNA sequencing, Yu et al. identified 16 molecularly distinct neuron types, detecting over 9,000 unique genes per neuron. This detailed molecular profiling revealed species-specific differences between human, macaque, and mouse dorsal root ganglion neurons, shedding light on the unique features of human sensory neurons, especially those related to pain and itch sensation. By employing spatial transcriptomics and microneurography, the study also linked the molecular signatures of neurons with their functional properties, such as temperature and chemical sensitivity.
Read more: https://www.nature.com/articles/s41593-024-01794-1
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Analysis of ventricular repolarization parameters and heart rate variability in obesity: a comparative study
Published in Scientific Reports
Tomar et al., are exploring how obesity influences cardiac function by examining ventricular repolarization parameters and heart rate variability. Using a sample of 90 Southeast Asian adults divided into normal, overweight, and obese categories, the researchers found that obese individuals exhibit prolonged QTc and Tpeak-Tend (Tpe) intervals, indicating altered cardiac electrophysiology. Obesity was also associated with reduced parasympathetic activity, evidenced by changes in heart rate variability parameters, while the QTc interval was significantly linked to heart rate variability, unlike the Tpe interval.
Read more: https://www.nature.com/articles/s41598-024-76580-x
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Social threat avoidance depends on action-outcome predictability
Published in Communications Psychology
How do humans avoid social threats? In their recent article, Sequestro et al., used virtual reality experiments to determine how participants would respond to a potentially threatening situation. Participants avoided angry avatars more frequently when they could predict the consequences of their actions, highlighting the role of goal-directed processes. However, avoidance also occurred in unpredictable scenarios, suggesting a contribution from stimulus-response associations. The research identifies two participant classes: a "goal-directed class," which showed higher avoidance only under predictability, and a "stimulus-response class," which avoided threats regardless of predictability. Physiological measures, including cardiac deceleration and muscular activity, further illustrated differences in decision-making processes between these classes. These findings emphasize the central role of action-outcome predictability in social threat avoidance and provide insights into the physiological and computational mechanisms underpinning this behavior.
Read more: https://www.nature.com/articles/s44271-024-00152-y
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AS160 is a lipid-responsive regulator of cardiac Ca2+ homeostasis by controlling lysophosphatidylinositol metabolism and signaling
Published in Nature Communications
Su et al., explores the role of AS160 in regulating calcium homeostasis in the heart, particularly in the context of obesity-related cardiac dysfunction. The study reveals that AS160, a Rab-GTPase activating protein, controls lysophosphatidylinositol metabolism and signaling, which is critical for calcium balance. In obesity, palmitic acid and a high-fat diet inhibit AS160's activity via NEK6-mediated phosphorylation, leading to increased Rab8a activity. This activation disrupts calcium homeostasis by promoting lysophosphatidylinositol metabolism, triggering calcium release from the sarcoplasmic reticulum, and impairing cardiac contractility. Mouse models with AS160 inactivation exhibit similar cardiac dysfunction, highlighting the AS160-lysophosphatidylinositol-Calcium axis as a potential therapeutic target for combating obesity cardiomyopathy.
Read more: https://www.nature.com/articles/s41467-024-54031-5
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