https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/294 2026-07-04T07:08:53Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/211881 Title: Hippocalcin Regulates NMDA Receptor Function and Neuronal Activity Through Elavl3 in Mouse Hippocampal Neural Precursor Cells Authors: Kang, Min-Jeong; Jung, Sung Jun; Son, Hyeon; Han, Joong-Soo; Park, Shin-Young Abstract: Hippocalcin (HPCA), a neuron-enriched calcium-binding protein, plays a critical role in brain function, but its role in neural precursor cells remains unclear. N-methyl-D-aspartate (NMDA) receptors are calcium-permeable glutamate receptors essential for neurodevelopment and synaptic plasticity, and their function has been implicated in neurological conditions. In this study, we investigated the role of HPCA in regulating NMDA receptor expression and function in mouse hippocampal neural precursor cells (mHNPCs). HPCA knockdown significantly reduced the expression of NMDA receptor-related genes, including Grin2C, Shank1, Serpine2, and selectively attenuated NMDA-induced calcium signaling. Transcriptomic analysis identified ELAV-like RNA-binding protein 3 (Elavl3), a neuron-enriched factor associated with neuronal activity, as a downstream candidate affected by HPCA knockdown. Consistently, Elavl3 suppression phenocopied HPCA deficiency, resulting in impaired NMDA receptor activity and reduced neuronal differentiation. Furthermore, hippocampal HPCA knockdown in vivo led to alterations in locomotor activity, contextual memory, and affective behaviors. Taken together, these findings demonstrate that HPCA supports NMDA receptor function and neuronal development, in part through Elavl3-associated pathways, and highlight HPCA as an important regulator of hippocampal function. 2026-03-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/210812 Title: Single-cell RNA Sequencing–Based analysis of diverse ion-channel transcripts across human CD4+ T-cell subsets Authors: Lee, Ji-min; Kim, Jintae; Kim, Woo-kyung; Kim, Hyun-jong Abstract: CD4+ T lymphocytes orchestrate adaptive immunity and diversify into helper and regulatory subsets that are selectively implicated in autoimmune and allergic diseases. Although ion channels are key determinants of lymphocyte activation and homeostasis, their subset-resolved expression patterns in human CD4+ T cells remain incompletely defined. Here, naïve CD4+ T cells were isolated from human peripheral blood mononuclear cells, polarized in vitro into Th1, Th2, Th17, and regulatory T (Treg) cells, and profiled by single-cell RNA sequencing (scRNA-seq). Unsupervised clustering resolved naïve and differentiated states and enabled subset annotation by canonical marker panels. Comparative analysis of an ion-channel/transporter gene panel revealed subset-biased transcript signatures, including differential representation of Ca2+-handling modules and membrane transport genes. Notably, Th2 showed enriched expression of ITPR1, Treg displayed relatively higher STIM2/ORAI3, and Th17 exhibited prominent AQP3 expression, alongside broad detection of core store-operated Ca2+ entry (SOCE) components across subsets. Collectively, these data provide a single-cell transcriptomic resource that delineates ion-transport landscapes across human CD4+ T-cell subset states and nominates candidate ionic regulators for follow-up mechanistic studies. 2026-02-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/210810 Title: Pharmacological activation of SERCA2 reverses ER calcium dysregulation and depression-like behaviors in hyperglycemic mice Authors: Lee, Huiju; Han, Yiseul; Song, Ju-Yeon; Kim, Do Gyeong; Chung, Heekyoung; Jung, Sung Jun; Son, Hyeon Abstract: Chronic hyperglycemia is linked to neuronal dysfunction and mood disorders, but the underlying molecular mechanisms remain unclear. In the present study, we examined the role of sarco/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2) in depression-like behaviors induced by hyperglycemia, using in vivo and in vitro models. Streptozotocin (STZ)-induced hyperglycemic mice exhibited elevated glucose levels and depression-like behaviors, along with increased hippocampal endoplasmic reticulum (ER) stress markers such as C/EBP homologous protein (CHOP), neuronal loss, and reduced SERCA2 expression. Human SH-SY5Y neuroblastoma cells exposed to high-glucose (40 mM) similarly showed decreased SERCA2, elevated ER stress markers, and impaired ER calcium homeostasis. Pharmacological activation of SERCA2 by CDN1163 suppressed ER stress and reversed depression-like behaviors in STZ mice; it also restored ER calcium levels in SH-SY5Y cells. Intrahippocampal infusion of SERCA2 inhibitor thapsigargin induced ER stress and depression-like behaviors without changing SERCA2 expression, indicating that SERCA2 dysfunction alone can trigger pathology. Treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) alleviated both molecular and behavioral alterations in hyperglycemic mice, supporting ER stress as a downstream effect of calcium dysregulation. These findings implicate hippocampal SERCA2 dysfunction as a central mechanism linking hyperglycemia to depression-like behaviors, highlighting SERCA2 as a potential therapeutic target. 2025-12-01T00:00:00Z https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/212594 Title: Extinction of contextual fear memory is facilitated in TRPM2 knockout mice Authors: Ko, Seung Yeon; Kim, Do Gyeong; Lee, Huiju; Jung, Sung Jun; Son, Hyeon Abstract: Transient receptor potential melastatin type 2 (TRPM2) is a nonselective cation channel involved in synaptic plasticity. We investigated its role in contextual fear conditioning and extinction of conditioned fear using Trpm2-deficient (Trpm2-/-) mice. Trpm2-/- mice exhibited reduced acquisition of contextual fear memory during conditioning but had an intact freezing response to conditioning context 24 h after conditioning. They also showed a reduced freezing response to extinction training, indicating facilitated extinction. Consistent with this, infusion of flufenamic acid (FFA), a TRPM2 antagonist, into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. The enhanced extinction in Trpm2-/- and FFA-treated mice was associated with down-regulation of immediate-early genes (IEGs) including Npas4, c-Fos, Arc and Egr1 in the hippocampus after extinction training. Our results indicate that TRPM2 plays a positive role in retention of contextual fear memory by modulating neuronal activity in the hippocampus, and suggest that TRPM2 activity could potentially be targeted to strengthen extinction-based exposure therapies for post-traumatic stress disorder (PTSD). 2025-12-01T00:00:00Z