情緒障礙是常見且重要的公共健康問題。越來越多的研究顯示，在幼年和青少年時期遭受社交忽視或同伴排擠等這類的遭遇，成年後容易產生躁鬱症或具有侵略性的反社會行為。這些情緒行為的表現方式也會依性別而產生不同變化。然而，哪些腦區與調節兒童受忽略而在成年後產生情緒障礙仍不清楚。本實驗目的為研究幼年時期遭遇忽略壓力對雄性和雌性小鼠腦中發生改變的腦區。我使用離乳後社交孤立12週和6週的小鼠來模擬孩童從小在生理和情感上被忽略。由於神經膠細胞在突觸結構的重塑中有著至關重要的作用，並且對大腦內的穩定功能非常敏感。因此，我利用免疫組織化學法染色離子鈣結合轉接分子（Iba1），用來尋找微小膠細胞的密度和面積發生改變的腦區。結果顯示，相對於群居組，離乳後獨居12週母鼠的紋狀體有較高的微小膠細胞密度，而且他們的內側中隔區有較小的微小膠細胞面積。接著，我以膠質纖維酸性蛋白（GFAP）和S100β 標示星狀膠細胞在上述腦區的變化。結果顯示，只有紋狀體在離乳後獨居12週的母鼠仍有顯著較高的星狀膠細胞密度和面積。但是公鼠不論是Iba1 、GFAP或是S100β 在群居和獨居小鼠之間皆沒有顯著差異。接下來，我將獨居時間縮短為6週，根據離乳後獨居12週的結果，針對紋狀體進行Iba-1和GFAP免疫組織化學法染色。結果顯示，微小膠細胞和星狀膠細胞在離乳後獨居6週小鼠腦中皆沒有顯著變化。以西方點墨法量化微小膠細胞活化指標CD11b 和 MHCII，以及神經元突觸相關蛋白PSD95、 synapsin和synaptophysin在紋狀體和伏隔核的表現量，發現離乳後獨居6週皆無顯著改變這些蛋白的量。綜上所述，我認為離乳後長期獨居會影響紋狀體的微環境，這在母鼠特別顯著，顯示紋狀體可能與離乳後長期獨居所造成的雌性特有的情緒障礙有關。

Mood disorders are critical health issues. Accumulating evidence has shown that individuals suffering from social negligence/isolation during childhood or adolescence are prone to bipolar disorder and aggressive antisocial behaviors in their adulthood and the characteristics of these emotional disturbances differ by gender. However, exactly which brain regions are involved in the pathogenesis of social isolation-related mood disorders remain relatively unclear. To address this issue, herein, I focused on identifying the brain regions changed by neglecting stress during childhood in male and female mice. I exposed the mice to a 12- or 6-week post-weaning isolation (PWI) to mimic the social isolation during childhood/adolescence. Since glial cells play a vital role in remodeling of synaptic structure and are sensitive to disturbances of homeostasis in the brain, the densities and morphologies of microglia and astrocytes after PWI in varied brain regions of male and female mice were examined. Results showed that the 12-week PWI increased densities of ionized calcium binding adaptor molecule 1 (Iba1), a marker for microglia, in the striatum but reduced the Iba-1 areas in the internal part of lateral septal nucleus of female mice. However, densities and areas of Iba-1 in selected regions of male mice were not affected by the 12-week PWI. Using glial fibrillary acidic protein (GFAP) and S100β to stain astrocytes, I found that the 12-week PWI also increased the striatal astrocytic density and area in female, but not male, mice. However, such changes in female mice were not evident after a 6-week PWI. The expressions of microglial activation markers, CD11b and MHCII, and neuronal synaptic proteins, PSD95, synapsin, and synaptophysin, in the striatum and nucleus accumbens were also not altered by the 6-week PWI. Taken together, my results showed that a 12-week PWI affected the microenvironment of striatum, especially in female mice, suggesting that the striatum might be involved in pathogenesis of female-specific mood disorders related to PWI.

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