阿茲海默疾病為一神經退化性疾病，且是最常見的失智症，好發於老年的族群，其在神經病理方面，最主要的特徵是由β類澱粉酶蛋白(Aβ)堆積所形成的老年斑塊。該疾病會使神經細胞退化，並導致患者記憶、認知和行為障礙，且約有30%的病會有焦慮、憂鬱等情緒疾病併發症。研究證實在阿茲海默病患，腦中缺氧與細胞自噬功能的失常會促進阿茲海默病患腦中的Aβ堆積進而加劇認知行為障礙及惡化病程，然而其中的機制目前仍有許多不清。過去的研究發現，高壓氧治療可以緩解神經性疾病導致的腦部損傷及恢復神經功能，藉由提升血氧濃度補足組織供氧不足的情況。因此，本研究主要探討高壓氧治療對阿茲海默疾病及其誘導情緒疾病和細胞自噬功能的改善。本研究利用9和12個月的雄性與雌性之APP/PS1基因轉殖型及野生型，進行不連續性1、2、4週和連續性4週高壓氧治療。首先觀察到APP/PS1基因轉殖鼠的認知記憶障礙和焦慮行為顯著上升，並且在海馬迴腦區的Aβ斑塊和細胞自噬之降解標記蛋白(p62)的表現量顯著增加，表示小鼠腦中細胞自噬功能失常。而不連續性4週高壓氧治療有助於緩解APP/PS1基因轉殖鼠的記憶缺失、焦慮和憂鬱行為和減少海馬迴中的Aβ斑塊透過改善細胞自噬的降解功能(觀察到海馬迴和杏仁核中的降解標記蛋白p62表現量顯著減少)。本研究結論:高壓氧治療可透過提升細胞自噬的降解功能，緩解阿茲海默疾病的認知記憶障礙及其誘導的焦慮和憂鬱行為。

Alzheimer’s disease (AD), the most common form of dementia, is mainly characterized by extracellular amyloid-ß (Aß) deposition leading to progressive neuronal loss and cognitive decline. In addition, mood disorder such as anxiety and depression are observed in nearly 30% of AD patients. Moreover, in AD patients, brain hypoxia and dysfunction of autophagy, a lysosome-mediated degradative pathway, were suggested to contribute to an accumulation and aggregation of Aβ in brains and aggravated AD progression. However, whether autophagy underlies hypoxia-related anxiety in AD remains unclear. Additionally, recent evidence suggested that hyperbaric oxygen (HBO) therapy, an increase of oxygen delivery to the brain is successfully used to treat brain injury and to restore neurological function. Therefore, we hypothesized that HBO is a beneficial strategy for treating AD and AD-mediated mood disorders via autophagy mechanism. 9 and 12 months old APP/PS1 mutant (AD) and wild-type mice (WT) were exposed to discontinuous 1,2,4 weeks and continuous 4 weeks HBO treatment. Our results revealed a severe cognition decline and increased anxiety as well as an increase of Aß deposition in aged-dependent AD mice. The male AD mice showed autophagy dysfunction through upregulation of p62 expression in the hippocampus (HF) and amygdala (AMG). Discontinuous 4 weeks HBO treatment improved anxiety and depression and dramatically decreased Aß deposition by enhancing autophagy degradation through a reduction of p62 expression in HF and AMG of AD mice. Taken together, these results suggested that HBO treatment ameliorates AD-mediated cognitive deficits and mood disorders by enhancing autophagy degradation.

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