青少年時期在生物體的中樞神經系統發展過程當中，屬於一個快速變化以及大腦神經網絡大規模重整的發育時期。因此，吾人臆測青少年生物體對於諸如壓力等外界刺激所導致的大腦結構、功能變化，可能與成年有異。但是支持此說法的科學證據仍然寥寥無幾。為探究此議題，本研究採用4週齡之青少年與8週齡之成年雄性大鼠做為動物模型，並於每日對兩週齡別的實驗大鼠施予相同的社交不穩定性壓力 (social instability stress)。長期壓力處理5週後，分析其中壓力處理中樞 － 杏仁核 (amygdala) 相關的學習記憶功能、神經元結構以及與神經可塑性相關的蛋白質表現量。藉由在各別週齡的實驗大鼠之間，直接比較相同的長期壓力處理對杏仁核之功能、結構與生化物質含量所造成之影響，來驗證假說。實驗結果顯示無論青少年抑或成年大鼠，在長期壓力處理的過程當中，相較於同齡控制組皆表現出攝食量減少與較低體重成長。此數據證明，吾人所使用的長期社交不穩定性壓力確實能引起大鼠的典型壓力反應。再者，本實驗採用與杏仁核高度相關的學習記憶評估工具，恐懼增益驚跳反應測試 (fear-potentiated startle test) ，來評量杏仁核相關的認知功能。數據顯示，於青少年時期經歷長期壓力的實驗大鼠相較於同齡的控制鼠在恐懼增益驚跳測試中有較差的表現，反之，成年壓力鼠相較於同齡控制鼠卻在測試中表現較好。接著，吾人利用單一神經元螢光標定 (single-neuron labeling) 技術來觀察杏仁核神經元的型態。結果顯示，於青少年時期經歷壓力的大鼠中，其杏仁核神經元的樹突叢聚數 (dendritic arborization) 與樹突突觸 (dendritic spine) 密度皆有明顯減少。相反地，長期社交不穩定性壓力經驗卻能增加成年大鼠杏仁核神經元的樹突叢聚數與突觸數量。進一步地，我們分析杏仁核中與認知功能以及神經可塑性相關的蛋白質表現量。西方墨點法結果指出，於青少年時期經歷壓力之大鼠杏仁核中，全長型 (full-length) 腦源性神經滋養因子 (brain-derived neurotrophic factor, BDNF) 受體TrkB、突觸標地融合蛋白 (synaptotagmin I, Syt I) ，以及重組突觸相關蛋白 (recombinant synaptosomal-associated protein 25kDa, SNAP-25) 等表現量，相較於同齡控制鼠皆有減少。反觀成年壓力鼠，杏仁核中全長型TrkB表現量則有所增加。最後，本研究藉由比較青少年組與成年組之控制鼠實驗數據，來觀察由9週齡正常成長至13週齡的過程當中，大鼠杏仁核相關功能與結構的變化。吾人發現，於此成長過程中，杏仁核神經元之長度較短的樹突數量減少、較長的樹突則持續延伸。並伴隨著樹突突觸分佈往遠端集中的現象。除此之外，13週齡控制鼠之杏仁核中全長型TrkB與截短型 (truncated) TrkB表現量也較9週齡來得多。 綜合以上所述，本實驗的數據說明長期社交不穩定性壓力對於不同週齡大鼠的杏仁核相關學習記憶表現有不同影響。而此現象可能是因為不同週齡大鼠在經歷長期壓力後，各自BDNF-TrkB機制途徑與神經可塑性改變不同所致。此外，研究結果也進一步指出，在青少年期間，尚未發育完全的杏仁核神經元之結構與功能，在面對外界長期壓力挑戰下是容易損壞的。反之，成熟的杏仁核神經元則對於外在壓力挑戰有較好的適應能力。

Adolescence is a time of developmental changes and reorganization in the brain, thus adolescents are likely to be more vulnerable than adults to the stress effects. However, scientific evidence in support of this hypothesis is still limited. We compared the stress effects on the amygdala experienced in adolescent (4-wk-old) rats to similar stress effects experienced in young adult rats (8-wk-old). Chronic social instability for 5 wks reduced food consumption and body weight gain in both age groups. However, this stress paradigm exerted opposite effects on fear-potentiated startle, an amygdala-dependent learning and memory task, in two groups, i.e., hampered the performance in adolescent group and improved it in adult group. Using a single neuron labeling technique, we found that the stress applied in adolescent rats reduced dendritic field and spine density in basal and lateral amygdala neurons. Yet opposite stress effects on neuron morphology were observed in adult rats. Moreover, stress in adolescence suppressed the amygdala expression of synaptic proteins, i.e., full-length TrkB, synaptotagmin I and SNAP-25. In adult rats, it enhanced full-length TrkB expression in the amygdala. Finally, the amygdala neuron morphology differed considerably between 9-wk-old and 13-wk-old control rats, i.e., showing less short dendrites, lengthened longest dendrite, and concentrated spines in the peripheral region. These age-dependent morphological changes were accompanied with local full-length and truncated TrkB upregulation. In summary, our results supported that chronic social instability exerts age-dependent effects on the fear-potentiated startle, possibly via altering BDNF-TrkB signaling and neuroplasticity in the amygdala. While amygdalar neuron development in the adolescent brain was hampered by the stress, mature neurons in the amygdala were capable of adapting to the stress.

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