Kim Young-Kook, Jo Danbi, Arjunan Archana, Ryu Yeongseo, Lim Yeong-Hwan, Choi Seo Yoon, Kim Hee Kyung, Song Juhyun
Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Jeollanamdo, Republic of Korea.
Biomedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun 58128, Jeollanamdo, Republic of Korea.
Int J Mol Sci. 2024 Feb 22;25(5):2567. doi: 10.3390/ijms25052567.
Alzheimer's disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer's disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer's disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer's disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue.
阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征是有多种病理表现,尤以β-淀粉样蛋白的聚集为显著标志。最近的研究揭示了过度肥胖与胶质细胞激活之间存在令人信服的关联,且这与认知障碍进一步相关。此外,在伴有记忆功能障碍的代谢性疾病患者中,胰岛素样生长因子1(IGF-1)水平也有改变的报道。因此,我们的研究致力于全面探索IGF-1在阿尔茨海默病背景下对海马体和脂肪组织的影响。为此,我们利用APP/PS2转基因小鼠进行了深入分析,该小鼠被公认为是阿尔茨海默病的一种成熟小鼠模型。对APP/PS2小鼠注射IGF-1后,我们观察到它们的行为模式有显著改变,这促使我们对海马体和脂肪组织进行全面的转录组分析。我们的数据揭示了这些组织功能谱的显著变化。具体而言,在海马体中,我们发现了与突触活动和神经炎症相关的变化。同时,脂肪组织在与脂肪褐变和细胞死亡信号相关的过程中表现出变化。除了这些发现,我们的分析还能够鉴定出一组长链非编码RNA和环状RNA,它们在注射IGF-1后表达有显著变化。此外,我们还努力预测这些已鉴定的RNA分子在我们研究背景下的潜在作用。总之,我们的研究为阿尔茨海默病模型中的海马体和脂肪组织提供了有价值的转录组数据,并提出了IGF-1在海马体和脂肪组织中都发挥着重要作用。