2022 神醫中心學術演講 6 (現場+視訊)
時間 : 上午11:00
地點 : 國衛院竹南院區/ 行政大樓B1第6會議室
主題 : Synaptic signature for emotional dysregulation disorder using rodent models
講師 : 林惠菁 教授
|視訊系統 Webex : 會議連結 密碼: 1234|
Emotional dysregulation disorder has great effect on the quality of life and generates economic burden globally. Mood dysregulation refers to the inability of a person to control their negative emotions, linked to various stressful experiences. Depression is usually triggered by external stress or stressful experiences. Two rodent models induced by different stressors, chronic social defeat stress (CSDS) exposure and tone-shock pairings, were used in our study. The synaptic plasticity and related mechanism are important regulators of stress in animal models. We aim to determine synapse functions and mechanism, including synaptic plasticity, synaptic receptors and related molecules, and spine morphology, in different stress reactions by rodent models.
First, depression-like behavior was observed in the susceptible group following chronic social defeat stress (CSDS) exposure, but not in stress-resistant group. Highfrequency stimulation-induced long-term potentiation (LTP) was impaired in the CSDS-induced depression-susceptible group. We demonstrated that synaptic plasticityrelated
molecules, such as brain-derived neurotrophic factor (BDNF) and phosphorylated cofilin, are important for synaptic function and structure in mice subjected to more stress.
Second, in rats received tone-shock pairings mimicking traumatic events, we found that traumatic stress induced depressive-like behaviors. Phosphorylation of extracellular signal-regulated kinases (ERKs) was altered in the amygdala and prefrontal cortex (PFC) of the tone-shock-related stress group. The levels of GluA1 and
PSD 95 were increased in the amygdala and decreased in the PFC of the tone-shockrelated stress group. Moreover, the glutamate-related abnormalities in the amygdala and PFC were normalized by ketamine treatment in the tone-shock-related stress group. In contrast, the depressive-like behaviors were not reversed by fluoxetine treatment in the
tone-shock-related stress group. These data demonstrated that traumatic stress leads to atypical antidepressant-resistant depressive symptoms through the glutamatergic system, and this rat model has potential to be a feasible animal model of antidepressantresistant depression. Application of intermittent theta-burst stimulation improved the altered synaptic plasticity, including LTP and long- term depression (LTD), and reversed the abnormal dendritic morphology in tone-shock-related stress animals.
Moreover, the BDNF and mammalian target of rapamycin (mTOR) signaling pathways were involved in the antidepressant mechanism of intermittent theta-burst stimulation. In summary, the synaptic plasticity and related molecules or signaling pathways are indeed involved in the pathophysiology and the therapeutic effect of depression in rodent models.
更新 : 2022-06-07
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