Possible link between the cognitive dysfunction associated with diabetes mellitus and the neurotoxicity of methylglyoxal

This study was designed to describe the relationship between methylglyoxal (MG) and the cognitive abilities of streptozotocin (STZ)-induced diabetic rats. Animal study revealed that the diabetic rats had significantly higher escape latency, a shorter average swimming time in the target quadrant and a longer average distance traveled to the platform in the Morris water maze compared with control group. The serum levels of MG in STZ rats were higher than in the control group and were positively correlated with the levels of serum glucose in the blood. In the STZ group, TUNEL-staining levels and the expression of cleaved Caspase-3 and Bax were significantly increased, whereas Bcl-2 expression was significantly decreased. Cell culture study showed that MG significantly increased the percentage of apoptotic hippocampal neurons. After the exposure to MG for 24 h, cleaved Caspase-3 and Bax expression increased, whereas Bcl-2 expression decreased. These data suggest a possible link between the cognitive dysfunction associated with diabetes mellitus and the neurotoxicity of MG, which may alter the expression levels of cleaved Caspase-3, Bcl-2 and Bax in the hippocampus.

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► STZ rats have cognitive dysfunction.
► The plasma MG levels in STZ rats is positively correlated with the plasma glucose levels.
► MG increases the expression of cleaved Caspase-3 and Bax.
► MG inhibits the expression of Bcl-2.
► MG induces apoptosis of cultured hippocampal neurons.