Abstract
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.
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Data used to support the findings of this study are available from the corresponding author upon request.
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This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), and National Institute of Science and Technology for Excitotoxicity and Neuroprotection (INCTEN/CNPq).
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C.A.G. and L.J.L. designed the study. L.J.L., K.M.W., L.R., L.D.B., E.B., and V.G.D. performed the laboratory experiments and collected data. L.J.L. and K. M. W. performed statistical analyses. C.A.G., L. J. L., K.M.W., and L.R. wrote the manuscript. All authors have edited and approved the manuscript.
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Lissner, L.J., Wartchow, K.M., Rodrigues, L. et al. Acute Methylglyoxal-Induced Damage in Blood–Brain Barrier and Hippocampal Tissue. Neurotox Res 40, 1337–1347 (2022). https://doi.org/10.1007/s12640-022-00571-x
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DOI: https://doi.org/10.1007/s12640-022-00571-x