Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats

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...

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Bibliographic Details
Published in:Neurochemical research 2021-02, Vol.46 (2), p.183-196
Main Authors: Lissner, Lílian Juliana, Rodrigues, Leticia, Wartchow, Krista Minéia, Borba, Ederson, Bobermin, Larissa Daniele, Fontella, Fernanda Urruth, Hansen, Fernanda, Quincozes-Santos, André, Souza, Diogo Onofre Gomes, Gonçalves, Carlos-Alberto
Format: Article
Language:English
Subjects:
Acute effects
Animals
Astrocytes
Astrocytes - drug effects
Behavior
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Central nervous system
Cerebrospinal fluid
Cognitive ability
Diabetes mellitus
Elevated Plus Maze Test
Evaluation
Gene expression
Glucose metabolism
Glutamate-ammonia ligase
Glutamatergic transmission
Glutamic Acid - metabolism
Glutamine
Glutathione
Glycolysis
Glycosylation
Hippocampus
Hippocampus - metabolism
Infusions, Intraventricular
Injection
Locomotion - drug effects
Locomotor activity
Long term memory
Male
Maze Learning - drug effects
Memory
Memory tasks
Memory, Long-Term - drug effects
Memory, Short-Term - drug effects
Mental task performance
Neurochemistry
Neurology
Neurosciences
Neurotransmission
Object recognition
Open Field Test - drug effects
Original Paper
Parameters
Proteins
Pyruvaldehyde
Pyruvaldehyde - administration & dosage
Pyruvaldehyde - toxicity
Rats
Rats, Wistar
S100b protein
Spatial analysis
Surgery
γ-Aminobutyric acid
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Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-020-03154-4