Fetal alcohol exposure is the most common known cause of preventable mental retardation, yet we know little about how microglia respond to, or are affected by, alcohol in vivo. Using an acute (single day) model of moderate (3 g/kg) to severe (5 g/kg) alcohol exposure in postnatal day (P) 7 or P8 mice we have found that alcohol-induced cortical neuroapoptosis is closely correlated in space and time with the appearance of activated microglia near dead cells. Microglia found in close proximity to dying neurons selectively engulfed those that were in later stages of apoptosis. Remarkably, most dead cells were cleared and microglia began to deactivate within 1-2 days of the initial insult. Coincident with microglial activation and deactivation, in the 5 g/kg alcohol model, there was a transient but substantial increase in pro-inflammatory factor (PIFs) expression. Work in BAX-null mice demonstrated that microglial activation and PIF expression were linked to BAX-dependent neuroapoptosis. As such, the level of microglial activation scaled with alcohol-induced cell death. Therefore, acute alcohol exposure in the developing cortex causes transient microglial activation and mobilization, promoting clearance of dead cells and tissue recovery. Moreover, cortical microglia show a remarkable capacity to rapidly deactivate following even severe neurodegenerative insults in the developing brain. Given that alcohol exposure on either P7 or P8 induced comparable levels of neuroapoptosis and microglial activation, we hypothesized that alcohol exposure on two sequential days (P7 and P8) would exacerbate neuroapoptosis and extend microglial activation. Instead, we found that the period of neuroapoptosis and microglial activation was similar after one day of alcohol exposure on P7 or after two days of exposure on P7 and P8. This was true for both the moderate and severe alcohol paradigms. Potentially, the low levels of cell death produced by the second day of injection may be due to neuroprotective mechanisms elicited by the first day of alcohol injection. In support of this idea, a preliminary microarray analysis of cortical gene expression 12 and 24 h after 5 g/kg alcohol exposure shows a decrease in expression of several pro-apoptotic factors and an increase in the expression of pro-survival factors, including neurotrophins. Of particular interest, BDNF, which has previously been shown to inhibit alcohol-induced neuroapoptosis, showed an eight-fold increase in expression at 24 h following 5 g/kg alcohol exposure and in situ hybridization showed strong BDNF expression near cortical regions with high levels of cell death. Future studies will be needed to extend the analysis of microglial activation states in this two-day injection model and to further explore the possibility that BDNF expression by microglia enacts neuroprotective mechanisms against a second insult. Finally, work in cell culture has suggested that chronic alcohol exposure may potentiate or inhibit microglial phagocytosis of dead cells. These studies raise the possibility that alcohol may directly affect microglial mobility which is important for their surveillance and synaptic remodeling functions. Therefore, we measured the effect of increasing doses of alcohol (0, 0.25, 0.5 and 1%) on microglial migration, branch motility, and morphology in dissociated BV-2 cell cultures and in acutely isolated neonatal (P5-6) brain slices. The results indicate that alcohol dose-dependently inhibits microglial migration and ruffling in cell culture, but in brain slices even high alcohol concentrations (0.5%) only reduce microglial branch motility by ~2%. When combined with our evidence for efficient microglial phagocytic clearance of dead cells in the neonatal cortex, these data suggest that while there is a measurable effect of acute alcohol exposure on microglial mobility, it does not impede microglia from performing their surveillance and phagocytic functions in vivo.

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本研究採用一項有關青少年成長與發展調適問題的長期貫時性追蹤資料(1996-1999)，試圖突破過去討論青少年憂鬱症狀發展時，所用之横斷式資料的囿限，嘗試應用潛在成長曲線模型(Latent growth curve model, LGC Model)的分析方法，加入歷史時間的縱深，捕捉青少年憂鬱症狀的「起始狀態」、與「個別的成長軌跡發展」。以不扭曲地將所有受試青少年在三年間的內化症狀變化情形，忠實地描述出來。而後，加入「改變」因素的討論，企圖尋找能影響青少年憂鬱症狀發展軌跡的關鍵機制。 此研究主要目的即在「具象化」復原力的理論觀點，企圖加入動態的時間面向，確認負向生活事件與青少年憂鬱症狀發展軌跡之間的因果關聯，並探討來自個人、與環境脈絡中的關係運作，對青少年憂鬱症狀平均數、變化方向與速率的跨時間影響。研究結果明確回答：為什麼有些青少年在受到憂鬱症狀的負向影響之後，尚能有回復機會並「表現地比預期好」的疑問。至於針對一群憂鬱症狀發展呈現改善、或惡化的少數青少年樣本，在性別、自尊、負向生活事件、家庭親子互動、學校好朋友關係等特性上的差異，本研究亦逐一說明。 在理論層次上，本項研究結合適切的研究方法，從「靜態」到「動態」地觀察青少年的身心發展、自「個人」到「家庭系統內外」討論內外在資源對青少年復原的短暫以及長久影響效果，並以一般青少年為研究對象的作法，擴增了復原力理論的推論範疇與解釋深廣。研究顯示，青少年的「改善」或「惡化」憂鬱症狀發展軌跡，確實在環境脈絡的節制之下，存在著個別差異。此外，青少年起始的憂鬱狀態並不影響憂鬱症狀軌跡發展的變化率。家庭經濟不利這項負向生活事件，對於青少年憂鬱症狀的預測，只呈現短暫的初始影響。自尊和好朋友關係皆是青少年可以主動建構與可為之舉，為兩個最重要能影響青少年憂鬱症狀變化的關鍵因素。至於學校脈絡，則可視為在家庭脈絡之外，能提供青少年憂鬱症狀改變效果的新路徑，以及讓青少年可以順利「轉大人」之雙重機會的結構因素。 / Using data derived from a panel study (1996-1999) of long-term Taiwanese adolescent development and adaptation, this study intended to break through the limitations of cross-sectional studies, which plagued past studies of adolescents’ developing depressive symptoms. By employing the Latent Growth Curve Model (LGC Model), this study mainly attempted to feature the individual initial status and the trajectory of every adolescent’s developmental depressive symptoms, which concerned about the important functions of the dynamic historical time and space on youth internalizing symptoms, for the research purpose to reflect the real resilient outcome each adolescent displayed. Besides, in order to understand the key factors that were taken as positive and effective mechanisms to influence the initial status and rates of changes on youth trajectories of depressive symptoms, several latent constructs such as self-esteem and protective factors developed from family and school contexts were taken into accounts. Further, specified characteristics were noted to highlight the basic differences gradually showed between resilient improved adolescents and worsen ones. A positive-psychological stance was taken as the leading research perspective in this study. The results shows that familial economic hardship only affects the initial status of adolescent depressive symptoms, implying that this negative event just had a short-term effect on youth’s psychological well beings. Those who were initially vulnerable to familial negative event had opportunity to become resilient over time. As to the protective factors, self-esteem and cohesive good-friendship were two crucial facets adolescents could actively construct and make efforts for further resilient performances to be better than expected. The analyzing results indicated, interestingly, that parent-child relationship early obtained in family context and adolescent’s satisfaction with parenting merely counted for the initial impact on adolescent trajectories of depressive symptoms. Concerns and cohesive relationships acquired in school contexts, especially in classes, provided dual chances for adolescents to become resilient in a long run.

La théorie des prérogatives de contrat administratif transplantée du droit administratif français a invoqué un débat de longue période dans la communauté judiciaire qu’une législation nationale unifiée a toujours été absente même aujourd’hui. En fait, dans le droit administratif français lié qui se compose principalement par la jurisprudence dans ce domaine, il y a non seulement une série de conditions préalables pour réaliser chaque prérogative, mais aussi un mécanisme de protection qui maintient un équilibre financier du contrat pour la justice finale. Or, sur la base d’une préférence pour les pouvoirs publics enracinée dans les traditions juridiques et le régime politique de la Chine, combinés certaines situations actuelles contemporaines, les chercheurs chinois ont partiellement mis en évidence la première, mais ignoré la seconde, conduisant à l’échec de cette transplantation juridique. En fait, comme une sorte de pouvoir administratif, la prérogative ne doit pas être considérée dans le propre système de contrat qui se compose par les droits et obligations consensuels, mais se réfère à la compétence légale de l’administration qui doit être contrôlée par la responsabilité légale. De plus, cela peut s’interpréter aussi comme la rupture de contrat, de sorte que l’administrateur doive prendre la responsabilité contractuelle fondée sur la théorie de la responsabilité sans faute, la relativité de contrat et la force de contrat, au lieu de la Légalité au sens étroit; la responsabilité administrative dans ce domaine devrait par conséquent être attribuée à la rupture de contrat, à l’endommagement et à l’illégalité. Peu importe quel modèle serait suivi par la législation à l’avenir, un système judiciaire indépendant et influant dans la pratique sociale sera la protection ultime de tous les systèmes juridiques incluant le contrat administratif en Chine. / The theory of prerogatives of administrative contract transplanted from the French administrative law has triggered such a longtime debate in the judicial community that a unified national legislation has been absent even today. Actually, in the French administrative law, composed mainly by Case Law in this domain, there is not only a series of conditions to enforce each prerogative, but also a protective mechanism to keep a financial balance of contract for the final justice. However, based on a preference to the Power rooted from the legal traditions and the political regime of China, combined with certain contemporary facts, Chinese researchers have partially highlighted the former but ignored the latter, leading to the failure of this legal transplant. Actually, as a type of administrative power, the prerogative should not be considered into the proper system of contract composed by the conventional rights and obligations, but refers to the legal authority of administration that should be controlled by the legal responsibility. In addition, it could be considered as the breach of contract too, so that the administrator should take the contractual responsibility based on the Theory of no-fault, on the Relativity of contract and on the Force effect of contract; thus the administrative responsibility hereof could be assumed for the breach of contract, for the quasi-tort out of contract and for the illegality. No matter which pattern would be followed by the future legislation in China, an independent and influential judicial system should be the final protection of all legal systems including the administrative contract.