講師資料
Talks：
IPCEF1-mediated NMDA receptor trafficking links IL-1β to epilepsy and cortical synchrony
IPCEF1 誘導之NMDA受體轉運在IL-1與癲癇和大腦皮質同步化所扮演的角色
Name：
張芳嘉（Fang-Chia Chang）
Position：
Distinguished Professor
Affiliation：
1. Department of Veterinary Medicine, National Taiwan University
2. Director General, National Center for Biomodels
Email：
Photo：
Research Interests：
Neuroimmunomodulation in sleep-wake regulation, neurological diseases (Parkinson’s disease, Alzheimer’s disease, epilepsy, stress, and posttraumatic stress disorder (PTSD))-related sleep disruptions and their neural circuits, novel therapeutic approaches for epilepsy, PTSD, Alzheimer’s disease and insomnia, herbal drug development and acupuncture therapy.
Selected Publications：
1. Yi-Jou Wu, Pei-Lu Yi, Fang-Chia Chang*. Effects of acupuncture at ST36 (Zusanli) on pain and associated sleep disturbance. Journal of Traditional and Complementary Medicine. 2025; in press. https://doi.org/10.1016/j.jtcme.2025.03.002
2. Yun Lo, Pei-Lu Yi, Yi-Tse Hsiao, Tung-Yen Lee, Fang-Chia Chang*. A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity. Communications Biology 2023; 6:716; https://doi.org/10.1038/s42003-023-05090-9
3. Yun Lo, Pei-Lu Yi, Yi-Tse Hsiao, Fang-Chia Chang*. Hypocretin in locus coeruleus and dorsal raphe nucleus mediates inescapable footshock stimulation (IFS)-induced REM sleep alteration. Sleep 2022; 45(3): zsab301; https://doi.org/10.1093/sleep/zsab301
Abstract：
Epilepsy is frequently accompanied by severe sleep disturbances, yet the molecular mechanisms linking neuroinflammation to both seizure generation and sleep dysfunction remain poorly understood. Here, we identified a neuroinflammatory signaling cascade that couples epileptogenesis with non-rapid eye movement (NREM) sleep disruption using a pentylenetetrazol (PTZ)-kindled mouse model of chronic epilepsy. We demonstrate that activation of interleukin-1β (IL-1β) signaling stimulates the phosphatidylinositol-3,4,5-trisphosphate (PIP3)–AKT–NF-κB pathway, leading to transcriptional upregulation of interaction protein for cytohesin exchange factors 1 (IPCEF1). Elevated IPCEF1 enhances synaptic membrane trafficking of N-methyl-D-aspartate receptors (NMDARs), particularly the GluN2B subunit, thereby promoting neuronal hyperexcitability, increasing seizure susceptibility, and impairing NREM slow-wave activity. Pharmacological inhibition of IL-1 receptors or PIP3–AKT signaling attenuated seizure severity and restored normal sleep architecture. Notably, IPCEF1 knockdown suppressed epileptic activity and rescued physiological NREM slow-wave synchronization without affecting total sleep duration, indicating that cortical synchrony can be selectively restored independent of sleep quantity. Together, these findings identify the IL-1β–PIP3–AKT–NF-κB–IPCEF1–NMDAR signaling axis as a mechanistic link between neuroinflammation, epileptogenesis, and sleep dysfunction, and establish IPCEF1 as a promising therapeutic target for simultaneously alleviating seizures and epilepsy-associated sleep comorbidities.
2026年會：