Gyu-Sang Hong

Background: Cell fate determination during brain development, encompassing both neural stem cells (NSCs) and immature neurons, is orchestrated by complex mechanical signals. While mechanical sensing during forebrain development is gaining recognition, the underlying regulatory genes remain underexplored. Results: In this study, we present a comprehensive analysis of the expression patterns of the mechanosensitive channel Tentonin 3 (TMEM150C, TTN3) across critical stages of embryonic brain development (E12.5, E14.5, E16.5, and E18.5) using RNAscope technology. We investigated Ttn3 expression in NSCs and immature neurons through co-staining with Nestin, Eomesodermin, and Doublecortin probes. Ttn3 transcripts were detected across multiple embryonic brain regions and layers, with a higher expression in the superficial layers compared to the ventricular and subventricular zones. In addition, we demonstrate that TTN3 is involved in the proliferation and migration of progenitor cells. Conclusions: Our findings suggest that TTN3 may play a critical role in embryonic brain development, potentially contributing as a mechanotransduction mediator.

Gold nanoparticles (AuNPs) are valuable tools in pharmacological and biological research, offering unique properties for drug delivery in the treatment of neurodegenerative diseases. This study investigates the potential of gold nanoparticles loaded with afzelin, a natural chemical extracted from Ribes fasciculatum, to enhance its therapeutic effects and overcome the limitations of using natural compounds regarding low productivity. We hypothesized that the combined treatment of AuNPs with afzelin (AuNP-afzelin) would remarkably enforce neuroprotective effects compared with the single treatment of afzelin. Central administration of AuNP-afzelin (10 ng of afzelin) indicated improvements in cognition and memory-involved assessments of behavioral tests, comparing single treatments of afzelin (10 or 100 ng of afzelin) in scopolamine-induced AD mice. AuNP-afzelin also performed superior neuroprotective effects of rescuing mature neuronal cells and recovered cholinergic dysfunction compared to afzelin alone, according to further investigations of BDNF-pCREB-pAkt signaling, long-term potentiation, and doublecortin (DCX) expression in the hippocampus. This study highlights the potential of afzelin with gold nanoparticles as a promising therapeutic approach for mitigating cognitive impairments associated with neurodegenerative diseases and offers a new avenue for future research and drug development.

Aim: This investigation addresses Piezo1's expression and mechanistic role in dorsal root ganglion (DRG) neurons and delineates its participation in mechanical and inflammatory pain modulation.Methods: We analyzed Piezo1's expression patterns in DRG neurons and utilized Piezo1‐specific shRNA to modulate its activity. Electrophysiological assessments of mechanically activated (MA) currents in DRG neurons and behavioral analyses in mouse models of inflammatory pain were conducted to elucidate Piezo1's functional implications. Additionally, we investigated the excitability of TRPV1‐expressing DRG neurons, particularly under inflammatory conditions.Results: Piezo1 was preferentially expressed in DRG neurons co‐expressing the TRPV1 nociceptor marker. Knockdown of Piezo1 attenuated intermediately adapting MA currents and lessened tactile pain hypersensitivity in models of inflammatory pain. Additionally, silencing Piezo1 modified the excitability of TRPV1‐expressing neurons under inflammatory stress.Conclusion: Piezo1 emerges as a key mediator in the transmission of mechanical and inflammatory pain, indicating its potential as a novel target for pain management therapies. Our finding not only advances the understanding of nociceptive signaling but also emphasizes the therapeutic potential of modulating Piezo1 in the treatment of pain.

Neurogenesis and interneuron integration are crucial for maintaining cortical circuit functionality. In the medial ganglionic eminences (MGE), ventral radial glia (vRG) predominantly generates somatostatin-expressing (SST+) interneurons through direct neurogenesis in the neocortex. However, the mechanism guiding vRG to asymmetrically divide and produce either SST+ interneuron or intermediate progenitor (IP) remains unclear. This study identifies a novel subpopulation of vRG, characterized by the expression of Anoctamin 1/TMEM16a (ANO1), a Ca2+-activated Cl− channel predominantly found in Fabp7+/Sox2+ vRGs. ANO1 deficiency significantly reduces vRG proliferation, disrupting the ratio of SST+ interneuron to IP, and correlates with changes in the number of parvalbumin-expressing interneurons. Electrophysiological recordings from E12.5 brain slices reveal that ANO1 modulates GABA-dependent Ca2+ influx via Orai1. This regulation is essential for directing the production of SST+ interneuron or IP during mouse forebrain development. Our findings provide novel insights into the Ca2+ regulatory mechanisms mediated by ion channels, underlying early neural development.

Malformation during cortical development can disrupt the balance of excitatory and inhibitory neural circuits, contributing to various psychiatric and developmental disorders. One of the critical factors of cortical neural networks is the fine regulation of neurogenesis through mechanical cues, such as shear stress and substrate stiffness. Piezo1, a mechanically-activated channel, serves as a transducer for these mechanical cues, regulating embryogenesis. However, specific cell-type expression patterns of this channel during cortical development have not yet been characterized. In the present study, we conducted an RNAscope experiment to visualize the location of Piezo1 transcripts with embryonic neuronal/glial lineage cell markers. Our analysis covered coronal sections of the mouse forebrain on embryonic day 12.5 (E12.5), E14.5, E16.5, and E18.5. In addition, applying Yoda1, a specific Piezo1 agonist, evoked distinct calcium elevation in piriform cortices of E16.5 and E18.5 embryonic slices. Furthermore, pharmacological activation or inhibition of this channel significantly modulated the migration of neurosphere-derived cells in vitro. These findings contribute valuable insights to the field of mechanobiology and provide an understanding of the intricate processes underlying embryonic brain development.