Title

麩胺酸系統在憂鬱症中可能的角色:以嗅球被切除之大鼠為動物模式所得的證據

Translated Titles

Possible Role of Glutamatergic System in Depressive Disorder: Evidence of Data from Olfactory Bulbectomized Rats

DOI

10.29478/TJP.200503.0002

Authors

何應瑞(Ying-Jui Ho);蔡元奮(Yuan-Feen Tsai)

Key Words

憂鬱症 ; 杏仁核 ; 動物模式 ; 麩胺酸神經系統 ; depression ; amygdala ; animal model ; glutamatergic system

PublicationName

臺灣精神醫學

Volume or Term/Year and Month of Publication

19卷1期(2005 / 03 / 01)

Page #

5 - 18

Content Language

繁體中文

Chinese Abstract

憂鬱症是盛行率相當高的精神疾病,由於不容易直接測量病患腦部之神經活性,因此藉由可資模擬的動物模式所得的研究結果,或將有助於瞭解形成憂鬱症可能的神經機轉。壓力是誘發憂鬱症的重要因子,研究上發現「噢球被切除之大鼠」(olfactory bulbectomized rats; OBX 大鼠)在受到壓力的環境中,其神經、免疫及內分泌反應之特徵與憂鬱症患者頗為相似,而且以抗憂鬱劑長期處理可以改善其生理及行為症狀,所以 OBX大鼠常作為研究憂鬱症的動物模式,其行為表現亦被廣泛作為篩選抗憂鬱劑之用。過去半個世紀以來,已經有相當多的研究探討大鼠的單肢類(monoamine)神經系統在嗅球被切除之後的變化。而近20無之研究結果亦發現麩膠酸(glutamate)神經系統在此動物模式中扮演著重要的角色。大鼠的嗅球投射麩腔酸神經纖維到杏仁核(amygdale),而杏仁核也有複雜的麩胺酸神經系統聯繫其他腦區,並且參與動物對壓力之反應。以電流刺激噢球,會抑制杏仁核內神經元之放電;若將嗅球切除,則會增加杏仁核內神經元的活性,並且降低杏仁核與大腦皮質內N-methyl-D-aspartate受體的密度。OBX大鼠在行為上會出現過度劇烈的壓力反應,同時其紋狀體(striatum)內麩胺酸之釋放量亦增加。若以全身性給藥或將藥物局部投入杏仁核內以阻斷麩胺酸神經訊遞,則可以改善其行為異常的症狀,這些結果顯示OBX大鼠出現對壓力的異常反應可能係杏仁核及麩胺酸神經系統功能的變化所導致,吾人據此推測人類的憂鬱症或其他對壓力反應異常疾病的病理機轉可能與此有關。

English Abstract

Direct investigation of the neuronal mechanism of depression in the human brain is difficult. Previous research has employed animal models to explore this issue. Stress is recognized as one of the important factors that can induce depression. The neuronal, immune, and endocrine responses of the olfactory bulbectomized (OBX) rats in a stressful environment have been shown to be similar to those in patients with depression. Since these responses in OBX rats can be alleviated by chronic treatment with antidepressants, this animal model of depression has been used to screen for the antidepressant-like activity of drugs. In the past half century, research in OBX rats have focused on the monoaminergic system, but data from the recent two decades indicate that the glutamatergic system plays an important role in depression. The amygdala is involved in the stress response. It not only receives the glutamatergic fibers from olfactory bulbs but also projects such fibers to a wide brain area. Electrical stimulation in the olfactory bulbs attenuates while olfactory bulbectomy increases the neuronal firing in the amygdala. A decreased N-methyl-D-aspartate receptor density in the cerebral cortex and the amygdala as well as an exaggerated behavioral response to the stress, accompanied by an enhanced striatal glutamate release, are observed in OBX rats. These abnormalities in behavior can be suppressed by systemic or locally drug treatment in the amygdala which antagonizes glutamatergic transmission. These findings suggest that the amygdala and the glutamatergic system are involved in the dysfunction of stress response in OBX rats, and that the similar systems play a role in the pathology of human depression and disorders of stress response. (Full text in Chinese)

Topic Category 醫藥衛生 > 社會醫學
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