憂鬱症是造成人類失能的主要原因之一。過去的研究發現，肥胖與代謝異常會增加罹患憂鬱症的風險，使其病症更為嚴重、持久，而且會降低抗憂鬱藥物的療效。在青少年階段，由於大腦還尚未發育完整，攝取過多的高脂飲食會使得大腦的結構和功能發生改變，加劇他們在這個年紀時行為決策和認知上的缺陷。憂鬱症的發病率有性別差異，通常女性罹患憂鬱症的比例是男性的1.5到2倍，但是導致性別差異的具體原因仍不明確。過去有關憂鬱症的動物研究，大多是以公鼠為研究模型，忽略了性別的因素。據此，本研究的目的是要探討青少年小鼠，長期攝食高脂飼料(high-fat diet, HFD) 後，是否會誘導出類似憂鬱症狀的行為，並且是否存在性別差異。我的研究結果顯示，離乳後的小鼠 (3周齡) 餵食HFD 8週後會誘導其表現出類憂鬱的行為，並且公鼠的憂鬱程度高於母鼠。檢視體重時，發現公鼠體重變化明顯高於母鼠。過去的研究表明，憂鬱症經常會伴隨著全身性的輕微發炎；而在大腦內，憂鬱症患者的內側前額葉皮質 (medial prefrontal cortex) 也常會出現發炎現象。然而，公、母鼠餵食8週HFD後，都沒有發現內側前額葉皮質有發炎的現象。另有研究指出，憂鬱症患者常有自主神經失衡的現象，也就是交感神經活性上升，而副交感神經活性下降。我以心率變異性 (heart rate variability) 測量餵食8週HFD的小鼠發現，公鼠的副交感神經活性下降，但在母鼠未見此結果。已知下視丘室旁核 (hypothalamic paraventricular nucleus) 內之催產素神經元對於調節自主神經和情緒障礙至關重要，所以我也針對此區的催產素神經元進行分析。結果表明，8週HFD並不會改變下視丘室旁核中的催產素神經元的數量或是其活性，而且未影響血漿中的催產素濃度。同時，下視丘室旁核中亦無發炎現象。總結我的研究，長期攝食HFD的青少年公鼠會表現出類憂鬱的行為，而母鼠則不明顯。此現象可能與公鼠攝食HFD後體重的增加明顯高於母鼠，以及副交感神經活性下降有關，但是具體原因仍需進一步探討。

Depression is one of the leading causes of disability globally. It has been shown that obesity and metabolic disorders not only elevate the risk and severity of depression but also reduce the effectiveness of antidepressant treatments. During adolescence, when the brain is still developing, excessive high-fat diet (HFD) consumption can cause structural and functional changes in the brain, worsening cognitive and decision-making deficits during this stage. Depression is known to exhibit differences between sexes, with women being 1.5 to 2 times more susceptible than men, although the exact mechanism remains unclear. Historically, animal studies on depression have predominantly used male animals, largely neglecting sex-specific factors. Thus, this study aimed to explore whether chronic HFD consumption induces depressive-like behavior in adolescent mice and whether such effects differ by sex. The results showed that feeding mice with HFD immediately after weaning (3 weeks old) for 8 weeks induced depression-like behavior, which was primarily observed in male mice but not female mice. Interestingly, male mice exhibited greater weight gain than females. Although depression is frequently linked to mild inflammation both systemically and in the medial prefrontal cortex, I did not find evidence of microglial activation in the medial prefrontal cortex of either male or female mice after the HFD regimen. Moreover, depression has been linked to autonomic imbalance, characterized by increased sympathetic activity and decreased parasympathetic activity. Through analysis of heart rate variability, I found that 8-week HFD reduced parasympathetic activity in male mice, but not in female mice. It is known that oxytocin neurons within the hypothalamic paraventricular nucleus (PVN) play a crucial role in regulating the autonomic nervous system and emotional disorders. Therefore, I also examined the expression of oxytocin neurons in this region. The results showed that neither the number nor activity of oxytocin neurons in the PVN, nor the levels of oxytocin in the plasma, were altered in the HFD mice. Additionally, there was no evidence of microglial activation in the PVN of these mice. In conclusion, long-term HFD consumption induced depression-like behaviors in adolescent male mice, with a less pronounced effect in female mice. This sex difference may be due to the greater increase in body weight and the decrease in parasympathetic nervous system activity in male mice compared to female mice after consuming the HFD. However, further research is needed to clarify the underlying mechanisms.

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