Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain

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 (3μmol/μL; subdivided into 6days) 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.

In vivo absorption and metabolism of leptosperin and methyl syringate, abundantly present in manuka honey

“…The main contributor of this activity is known to be methylglyoxal, a highly reactive dicarbonyl compound, which is transformed from dihydroxyacetone present in the nectar of the flower . Since methylglyoxal is also inevitably formed as a by‐product of glycolysis and/or from nonenzymatic glycation and lipid peroxidation, it may be associated with several pathologies such as diabetes and neurodegenerative diseases ; however, it is reported that the intake of methylglyoxal by ingestion of manuka honey is probably safe for consumption by healthy individuals . The ingested methylglyoxal is covalently adducted to digestion enzymes or detoxified by the glyoxalase system .…”

Glycolysis-Derived Compounds From Astrocytes That Modulate Synaptic Communication

“…Elevated MG seems to increase the expression of astrocyte markers (glial fibrillary acidic protein – GFAP and S100B) and cytokines in astrocyte culture and in vivo , leading to astrogliosis and neuroinflammation (Chu et al, 2016). However, cognitive impairment has also been reported without changes in classical parameters of astrogliosis (Hansen et al, 2016b). Impairment in glucose flow and/or dysfunction of the glyoxalase system is a common and early event in neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s diseases (PD).…”

1400 W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia

“…Each arm had different cues for distinction from each other. Y-maze testing consisted of two trials separated by an interval of 1h [37,38] . In the first trial (training), the animal was placed at the end of one arm and allowed access to that arm and another arm for 10 min.…”