Dos Santos Tiago Marcon, Ramires Júnior Osmar Vieira, Alves Vinícius Santos, Coutinho-Silva Robson, Savio Luiz Eduardo Baggio, Wyse Angela T S
Wyse's Lab, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Rua Ramiro Barcelos, 2600-Anexo, 90035-003 Porto Alegre, RS, Brazil.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro - UFRJ, Av. Carlos Chagas Filho, 373, CCS, Ilha do Fundão, 21941-902 Rio de Janeiro, RJ, Brazil.
Life Sci. 2021 Jul 15;277:119386. doi: 10.1016/j.lfs.2021.119386. Epub 2021 Mar 24.
Homocysteine has been linked to neurodegeneration and motor function impairments. In the present study, we evaluate the effect of chronic mild hyperhomocysteinemia on the motor behavior (motor coordination, functional performance, and muscular force) and biochemical parameters (oxidative stress, energy metabolism, gene expression and/or protein abundance of cytokine related to the inflammatory pathways and acetylcholinesterase) in the striatum and cerebellum of Wistar male rats.
Rodents were submitted to one injection of homocysteine (0.03 μmol Hcy/g of body weight) between 30th and 60th postnatal days twice a day. After hyperhomocysteinemia induction, rats were submitted to horizontal ladder walking, beam balance, suspension, and vertical pole tests and/or euthanized to brain dissection for biochemical and molecular assays.
Chronic mild hyperhomocysteinemia did not alter motor function, but induced oxidative stress and impaired mitochondrial complex IV activity in both structures. In the striatum, hyperhomocysteinemia decreased TNF-α gene expression and increased IL-1β gene expression and acetylcholinesterase activity. In the cerebellum, hyperhomocysteinemia increased gene expression of TNF-α, IL-1β, IL-10, and TGF-β, while the acetylcholinesterase activity was decreased. In both structures, hyperhomocysteinemia decreased acetylcholinesterase protein abundance without altering total p-NF-κB, NF-κB, Nrf-2, and cleaved caspase-3.
Chronic mild hyperhomocysteinemia compromises several biochemical/molecular parameters, signaling pathways, oxidative stress, and chronic inflammation in the striatum and cerebellum of rats without impairing motor function. These alterations may be related to the mechanisms in which hyperhomocysteinemia has been linked to movement disorders later in life and neurodegeneration.
同型半胱氨酸与神经退行性变和运动功能损害有关。在本研究中，我们评估慢性轻度高同型半胱氨酸血症对Wistar雄性大鼠纹状体和小脑中运动行为（运动协调性、功能表现和肌肉力量）以及生化参数（氧化应激、能量代谢、与炎症途径相关的细胞因子的基因表达和/或蛋白质丰度以及乙酰胆碱酯酶）的影响。
在出生后第30至60天之间，每天给啮齿动物注射一次同型半胱氨酸（0.03 μmol Hcy/克体重），共注射两次。诱导高同型半胱氨酸血症后，对大鼠进行水平阶梯行走、横梁平衡、悬吊和垂直杆测试，和/或实施安乐死以进行脑解剖，用于生化和分子分析。
慢性轻度高同型半胱氨酸血症未改变运动功能，但在两个结构中均诱导了氧化应激并损害了线粒体复合物IV的活性。在纹状体中，高同型半胱氨酸血症降低了TNF-α基因表达，增加了IL-1β基因表达和乙酰胆碱酯酶活性。在小脑中，高同型半胱氨酸血症增加了TNF-α、IL-1β、IL-10和TGF-β的基因表达，而乙酰胆碱酯酶活性降低。在两个结构中，高同型半胱氨酸血症均降低了乙酰胆碱酯酶蛋白丰度，而未改变总p-NF-κB、NF-κB、Nrf-2和裂解的caspase-3。
慢性轻度高同型半胱氨酸血症损害了大鼠纹状体和小脑中的多个生化/分子参数、信号通路、氧化应激和慢性炎症，但未损害运动功能。这些改变可能与高同型半胱氨酸血症在生命后期与运动障碍和神经退行性变相关的机制有关。
