Uzor Ndidi-Ese, Scheihing Diego Morales, Kim Gab Seok, Moruno-Manchon Jose Felix, Zhu Liang, Reynolds Caroline R, Stephenson Jessica M, Holmes Aleah, McCullough Louise D, Tsvetkov Andrey S
University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA; Department of Neurology, the University of Texas McGovern Medical School at Houston, Houston 77030, TX, USA.
Department of Neurology, the University of Texas McGovern Medical School at Houston, Houston 77030, TX, USA.
Mol Cell Neurosci. 2020 Sep;107:103536. doi: 10.1016/j.mcn.2020.103536. Epub 2020 Aug 7.
Peroxisomes exist in nearly every cell, oxidizing fats, synthesizing lipids and maintaining redox balance. As the brain ages, multiple pathways are negatively affected, but it is currently unknown if peroxisomal proteins are affected by aging in the brain. While recent studies have investigated a PEX5 homolog in aging C. elegans models and found that it is reduced in aging, it is unclear if PEX5, a mammalian peroxisomal protein that plays a role in peroxisomal homeostasis and degradation, is affected in the aging brain. To answer this question, we first determined the amount of PEX5, in brain homogenates from young (3 months) and aged (26 through 32+ months of age) wild-type mice of both sexes. PEX5 protein was decreased in aged male brains, but this reduction was not significant in female brains. RNAScope and real-time qPCR analyses showed that Pex5 mRNA was also reduced in aged male brain cortices, but not in females. Immunohistochemistry assays of cortical neurons in young and aged male brains showed that the amount of neuronal PEX5 was reduced in aged male brains. Cortical neurons in aged female mice also had reduced PEX5 levels in comparison to younger female mice. In conclusion, total PEX5 levels and Pex5 gene expression both decrease with age in male brains, and neuronal PEX5 levels lower in an age-dependent manner in the cortices of animals of both sexes.
过氧化物酶体几乎存在于每一个细胞中，负责氧化脂肪、合成脂质并维持氧化还原平衡。随着大脑衰老，多种途径会受到负面影响，但目前尚不清楚过氧化物酶体蛋白是否会受到大脑衰老的影响。虽然最近的研究在衰老的秀丽隐杆线虫模型中研究了一种PEX5同源物，并发现其在衰老过程中减少，但尚不清楚在过氧化物酶体稳态和降解中起作用的哺乳动物过氧化物酶体蛋白PEX5在衰老大脑中是否会受到影响。为了回答这个问题，我们首先测定了来自年轻（3个月）和老年（26至32个月以上）野生型雌雄小鼠脑匀浆中PEX5的含量。老年雄性小鼠大脑中的PEX5蛋白减少，但这种减少在雌性小鼠大脑中并不显著。RNAScope和实时定量PCR分析表明，老年雄性小鼠大脑皮质中的Pex5 mRNA也减少，但雌性小鼠中没有。对年轻和老年雄性小鼠大脑皮质神经元的免疫组织化学分析表明，老年雄性小鼠大脑中神经元PEX5的含量减少。与年轻雌性小鼠相比，老年雌性小鼠皮质神经元中的PEX5水平也降低。总之，雄性大脑中PEX5的总水平和Pex5基因表达均随年龄增长而降低，并且在两性动物的皮质中，神经元PEX5水平以年龄依赖性方式降低。
