Biochemistry Graduate Program, Universidade Federal Do Rio Grande Do Sul (UFRGS), Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035003, Brazil.
Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center (UTHealth), Houston, TX, USA.
Neurotox Res. 2022 Oct;40(5):1337-1347. doi: 10.1007/s12640-022-00571-x. Epub 2022 Sep 3.
Methylglyoxal (MG) is a reactive dicarbonyl compound formed mostly via the glycolytic pathway. Elevated blood glucose levels can cause MG accumulation in plasma and cerebrospinal fluid in patients with diabetes mellitus and Alzheimer's disease. Under these disease conditions, the high reactivity of MG leads to modification of proteins and other biomolecules, generating advanced glycation end products (AGEs), which are considered mediators in neurodegenerative diseases. We investigated the integrity of the blood-brain barrier (BBB) and astrocyte response in the hippocampus to acute insult induced by MG when it was intracerebroventricularly administered to rats. Seventy-two hours later, BBB integrity was lost, as assessed by the entry of Evans dye into the brain tissue and albumin in the cerebrospinal fluid, and a decrease in aquaporin-4 and connexin-43 in the hippocampal tissue. MG did not induce changes in the hippocampal contents of RAGE in this short interval, but decreased the expression of S100B, an astrocyte-secreted protein that binds RAGE. The expression of two important transcription factors of the antioxidant response, NF-κB and Nrf2, was unchanged. However, hemeoxigenase-1 was upregulated in the MG-treated group. These data corroborate the idea that hippocampal cells are targets of MG toxicity and that BBB dysfunction and specific glial alterations induced by this compound may contribute to the behavioral and cognitive alterations observed in these animals.
甲基乙二醛（MG）是一种反应性二羰基化合物，主要通过糖酵解途径形成。高血糖水平可导致糖尿病和阿尔茨海默病患者的血浆和脑脊液中 MG 积累。在这些疾病条件下，MG 的高反应性导致蛋白质和其他生物分子的修饰，产生晚期糖基化终产物（AGEs），被认为是神经退行性疾病的介质。我们研究了 MG 经侧脑室给药对大鼠急性损伤时血脑屏障（BBB）的完整性和海马星形胶质细胞反应。72 小时后，BBB 完整性丧失，通过 Evans 染料进入脑组织和脑脊液中的白蛋白以及海马组织中水通道蛋白-4 和连接蛋白-43 的减少来评估。在这个短时间间隔内，MG 没有诱导海马组织中 RAGE 的变化，但降低了 S100B 的表达，S100B 是一种与 RAGE 结合的星形胶质细胞分泌蛋白。抗氧化反应的两个重要转录因子 NF-κB 和 Nrf2 的表达不变。然而，血红素加氧酶-1 在 MG 处理组中上调。这些数据证实了海马细胞是 MG 毒性的靶标这一观点，并且该化合物引起的 BBB 功能障碍和特定的神经胶质改变可能导致这些动物中观察到的行为和认知改变。
