Abstract
Methylglyoxal (MG) is a by-product of glycolysis. In pathological conditions, particularly diabetes mellitus, this molecule is unbalanced, causing widespread protein glycation. In addition to protein glycation, other effects resulting from high levels of MG in the central nervous system may involve the direct modulation of GABAergic and glutamatergic neurotransmission, with evidence suggesting that the effects of MG may be related to behavioral changes and glial dysfunction. In order to evaluate the direct influence of MG on behavioral and biochemical parameters, we used a high intracerebroventricular final concentration (3 μM/μL) to assess acute effects on memory and locomotor behavior in rats, as well as the underlying alterations in glutamatergic and astroglial parameters. MG induced, 12 h after injection, a decrease in locomotor activity in the Open field and anxiolytic effects in rats submitted to elevated plus-maze. Subsequently, 36 h after surgery, MG injection also induced cognitive impairment in both short and long-term memory, as evaluated by novel object recognition task, and in short-term spatial memory, as evaluated by the Y-maze test. In addition, hippocampal glutamate uptake decreased and glutamine synthetase activity and glutathione levels diminished during seventy-two hours after infusion of MG. Interestingly, the astrocytic protein, S100B, was increased in the cerebrospinal fluid, accompanied by decreased hippocampal S100B mRNA expression, without any change in protein content. Taken together, these results may improve our understanding of how this product of glucose metabolism can induce the brain dysfunction observed in diabetic patients, as well as in other neurodegenerative conditions, and further defines the role of astrocytes in disease and therapeutics.
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The data used to support the findings of this study are available from the corresponding author upon request.
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Acknowledgments
The authors gratefully acknowledge 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 Instituto Nacional de Ciência e Tecnologia para Excitoxicidade e Neuroproteção (INCTEN/CNPq).
Contribution Statement
F.H., C.A.G. and L.J.L. designed the study. L.J.L., E.B., L.R., K.M.W., L.D.B., F.U.F., F.H performed laboratory experiments and collected data. L.J.L. and K.M.W performed statistical analyses. F.H., C.A.G., L.J.L, K.M.W., L.D.B and L.R. wrote the manuscript. All authors edited and approved the manuscript.
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Lissner, L.J., Rodrigues, L., Wartchow, K.M. et al. Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats. Neurochem Res 46, 183–196 (2021). https://doi.org/10.1007/s11064-020-03154-4
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DOI: https://doi.org/10.1007/s11064-020-03154-4