Elsevier

Physiology & Behavior

Volume 164, Part A, 1 October 2016, Pages 93-101
Physiology & Behavior

Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain

https://doi.org/10.1016/j.physbeh.2016.05.046Get rights and content
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Highlights

  • Sustainable ICV infusion of MG (6 days) in rats induces a cognitive deficit.

  • A single high-dose MG infusion (1 day) reduces anxiety-like behavior in rats.

  • MG causes persistent alterations in the hippocampus, but not in the frontal cortex.

  • MG infusion modifies GLO1 activity, AGEs content and glutamate uptake.

Abstract

Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3 μmol/μL; subdivided into 6 days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

Keywords

Advanced glycation end products
Anxiety
Dementia
Diabetes
Glyoxalase 1
Methylglyoxal

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