自閉症的主要行為特徵是社會行為障礙。有研究指出在懷孕期間服用丙戊酸可能影響神經管之形成而引發自閉症。愈來愈多證據顯示自閉症某些分子的異常會影響其神經突觸或神經可塑性之機轉。除了當前小鼠行為模式研究似自閉症行為可能有成果的評估自閉症相關大腦異常實驗方法外，我們將利用大鼠在懷孕期間曝露於丙戊酸（VPA）以建立自閉症動物模型，觀察是否其行為的特點與自閉症之行為相似，用嘗試利用藥物治療改善其行為。目前的結果顯示，在母鼠懷孕期間投與丙戊酸所生下之子代出現了社會行為障礙之現象，且在高架十字迷宮測試當中也觀察到母鼠懷孕期間投與丙戊酸所生下之子代出現較焦慮之情況，但和投與生理食鹽水所產下之子代其移動行走距離並無顯著差異(開放空間行為測試)。進一步探討其母鼠照護行為是否為造成自閉症老鼠社會行為障礙之關聯性。在產後交叉飼養實驗中，母鼠懷孕期間投與丙戊酸所生下之子代之社會行為障礙並不能得到改善。在母鼠懷孕期間投與丙戊酸所生下之子代發現高度恐懼記憶並出現恐懼制約學習抹除障礙。而D-環絲氨酸（DCS），是NMDA 接受器之甘胺酸鍵結位置的藥物，用以促進恐懼制約學習抹除及社會恐懼焦慮症。母鼠懷孕期間投與丙戊酸所生下之子代身上投與DCS可以觀察到其社會行為障礙有獲得改善之趨勢。此動物行為模式將成為瞭解及治療自閉症的工具，並可設計出一治療方法來減少自閉症神經和行為上的異常。

Autism presents social deficit. Recent studies demonstrated prenatal exposure to VPA during the critic period of neural tube formation leaded to autistic phenotypes. Accumulating evidence suggested that some molecular defects in autism may interfere with the mechanisms of synapse maturation and plasticity. A challenging but potentially fruitful approach to evaluate proposed brain abnormalities for autism is to study analogous behaviors in mouse models. In this project I aim to establish the animal model of autism by prenatal exposure to valproate (VPA) to test behavioral tasks analogies to the features of autism and survey the electrophysiological features of brain area involving aberrant behavior. Current results showed the offspring of VPA-treated dams exhibited impaired social interaction and were more anxious in the elevated plus-maze, but had normal broad locomotion (distance moved and velocity).In addition, offspring of VPA-treated dams revealed high fear memories and impaired fear extinction. In postnatal cross-fostering, the state of social deficit of offspring of VPA-treated dams can not be improved. D-cycloserine (DCS), a partial agonist at the glycine recognition site on NMDA receptor complex, to promote conditioned fear extinction and improve social anxiety disorder. Offspring of VPA-treated dams treated by DCS trended to improve their social deficit. The model could be a valuable tool, besides the understanding and treatment of the disorder itself, to design therapeutic interventions that minimize the neurological and behavioral abnormalities caused by this disease.

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