對於壓力的定義，目前並沒有一致性的認知。一般認為會嚴重地影響個體生理及心理恆定性的物件或情況，都能定義為「壓力」，其影響的程度可從較輕度的焦慮行為，到一些經歷重度創傷所造成的身心失調等現象。而當個體遭遇到壓力的時候，一些生理的調節機制可以產生立即的急性反應來適應環境，以維持個體的生存；然而過度或長期的表現此反應機制，反而會對於正常的生理機能造成不良的影響。而在過去許多的動物實驗及臨床的觀察研究中，都發現到壓力對於中樞系統認知功能的表現有著很大的影響，且其影響的程度隨著壓力的強度及個體的差異有著兩極化（biphasic）的現象；例如短暫且輕度的壓力會促進記憶的形成，但是過度及長期的壓力反而會造成神經元的損傷，而破壞了學習記憶的表現。然而，對於壓力如何影響突觸塑性其中的細胞和分子機制依然不明。最近的研究指出在海馬迴CA1區域的長期增益現象（Longterm potentiation；LTP）其機制會隨著發育過程而轉變，但究竟是哪些生理因子參予這個發育的轉變仍然沒有定論。我們的研究發現輕度的壓力模式（將新生幼鼠和母鼠分離）會影響海馬迴 CA1區域長期增益現象誘發機制的改變，其主要係透過活化與壓力反應有關的促皮質素釋放因子（corticotrophin-releasing factor，CRF）的系統，進而加速海馬迴CA1區域的長期增益現象由cyclic AMP-dependent protein kinase (PKA)依賴性型式轉變成Ca2+/calmodulin-dependent protein kinase II (CaMKII)的依賴性的型式。此外藉由反轉錄酶-聚合反應（reverse transcriptase-polymerase chain reaction，RT-PCR）的結果也發現，將新生幼鼠和母鼠分離的壓力似乎是藉由增加CaMKII基因的轉錄而進行調控。此外我們也利用離體的海馬迴神經細胞組織培養証實CRF的確可以增加CaMKII的表現，此一作用會被不具選擇性的CRF受體拮抗劑astressin及CRF第一型受體的專一性拮抗劑NBI27914及PKA的拮抗劑KT5720所阻斷，但不會受CRF第二型受體的專一性拮抗劑K41498及protein kinase C（PKC）的拮抗劑bisindolylmaleimide I影響。研究結果顯示在海馬迴CA1區域中CRF可能扮演在發育早期參與調控神經功能的角色。此外，適度的壓力可以透過促進荷爾蒙分泌，活化影響長期增益現象誘發所需的訊息傳遞路徑，而加速發育過程中海馬迴區域突觸塑性的成熟。

The term “stress” is generally defined in biological systems as any condition that seriously perturbs physiological and psychological homeostasis ranging from anxiety to posttraumatic stress disorder. With regard to stress effects on CNS, extensive evidence from animal and human studies indicates that psychological stress has a biphasic influence on cognitive function depending on the severity and context. Brief periods of stress could promote memory formation, whereas more severe or prolonged stressors can exhibit marked deficits in various learning and memory tasks. However, little is known about how it does so. Recent data suggest that the mechanisms underlying long-term potentiation (LTP) in the CA1 region of the hippocampus vary with developmental age. The physiological factors regulating this developmental change, however, have not yet been elucidated. Here we show that mild neonatal maternal separation accelerates the developmental switch in the signaling cascades for hippocampal CA1 LTP induction from a cyclic AMP-dependent protein kinase (PKA)- to a Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent pattern via the activation of corticotrophin-releasing factor (CRF) system. Furthermore, this action appears to be mediated through an increased transcription of the  isoform of CaMKII (CaMKII) gene. We also demonstrate that application of CRF to cultured hippocampal neurons significantly increases the expression of CaMKII, which is blocked by the non-specific CRF receptor antagonist, astressin, and specific CRF receptor 1 antagonist, NBI27911, and PKA inhibitor, KT5720, but not by the CRF receptor 2 antagonist, K41498, or protein kinase C inhibitor, bisindolylmaleimide I. These results suggest a novel role for CRF in regulating early developmental events in the hippocampus and indicate that although maternal deprivation is stressful for neonate, appropriate neonatal maternal separation can serve to promote an endocrine state that fosters the rate of maturation of the signaling cascades underlying the induction of LTP in developing hippocampus.

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