Talks：

IL-1-Src family kinases pathway in epileptogenesis and epilepsy-induced sleep disruptions

Name：

張芳嘉(Fang-Chia Chang)

Position：

Professor

Affiliation：

Department of Veterinary Medicine Graduate Institute of Brain and Mind Sciences National Taiwan University

Email：

fchang@ntu.edu.tw

Photo：

Research Interests：

Neuroimmunomodulation on sleep, stress and sleep, epilepsy-induced sleep disruptions, acupuncture on insomnia

Selected Publications：

1. Tzu-Rung Huang, Shuo-Bin Jou, Yu-Ju Chou, Pei-Lu Yi, Chun-Jen Chen, Fang-Chia Chang*. Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption. BMC Neuroscience 2016; 17:74. 2. Pei-Lu Yi, Chin-Yu Lu, Shuo-Bin Jou, Fang-Chia Chang*. Low-frequency electroacupuncture suppresses focal epilepsy and improves epilepsy-induced sleep disruptions. Journal of Biomedical Science 2015; 22:49 3. Yi-Tse Hsiao, Pei-Lu Yi, Chiung-Hsiang Cheng, Fang-Chia Chang*. Disruption of footshock-induced theta rhythms by stimulating median raphe nucleus reduces anxiety in rats. Behavioural Brain Research 2013; 247:193-200. 4. Pei-Lu Yi, Ying-Ju Chen, Chung-Tien Lin, Fang-Chia Chang*. Occurrence of epilepsy at different zeitgeber times alters sleep homeostasis differently in rats. Sleep 2012; 35(12):1651-1665. 5. Yi-Tse Hsiao, Pei-Lu Yi, Chia-Ling Li, Fang-Chia Chang*. Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology 2012; 62:373-384.

Abstract：

In this presentation, we tried to elucidate the effects of IL-1-Src family kinases pathway in epileptogenesis, astrogliosis, microgliosis, neurodegeneration, neurogenesis, and sleep disruptions, when a low dose of pentylenetetrazol (PTZ) was systemically injected to cause the spontaneous epilepsy. The spontaneously generalized seizures were induced by intraperitoneal injection of low dose PTZ, the sleep-wake activity was analyzed, and the seizure threshold was determined in both the wildtype and IL-1R1 KO mice. The expression of subunit proteins of NMDA receptor, NR1 and phosphorylated-NR2B (at Tyr1472) were determined in the frontal cortex, hypothalamus and hippocampus by the Western blotting. The expressions of astrocytes and microglia, neurogenesis and neurodegeneration were determined. By employing IL-1 receptor type-1 knockout (IL-1R1 KO) mice, IL-1 was found to increase astrogliosis, microgliosis and neurogenesis, but not neurodegeneration, which contribute to epileptogenesis. IL-1R1 activates NF-B and Src family kinases to increase the NR1 subunit of NMDA receptor and phosphorylate NR2B, respectively. Src family kinases activator in IL-1R1 KO mice restored IL-1 signal and increase phosphorylated NR2B to decrease epileptic threshold and disrupt sleep; in contrast, Src family kinases inhibitor administered into wildtype mice mimicked IL-1R1 KO mice to reduce phosphorylated NR2B to increase epileptic threshold and blocked epilepsy-induced sleep disturbance. NF-B activator in IL-1R1 KO mice enhanced epileptogenesis and reappeared epilepsy-induced sleep disruption; administration of NF-B inhibitor into wildtype epileptic mice reduced epilepsy and diminished sleep disturbance. These results demonstrate underlying mechanisms of IL-1 in epileptogenesis and sleep disruption.