Methylglyoxal (MG) and Cerebro-Renal Interaction: Does Long-Term Orally Administered MG Cause Cognitive Impairment in Normal Sprague-Dawley Rats?
Kimio Watanabe,
Kana Okada,
Ryoji Fukabori,
Yoshimitsu Hayashi,
Koichi Asahi,
Hiroyuki Terawaki,
Kazuto Kobayashi,
Tsuyoshi Watanabe,
Masaaki Nakayama
Affiliations
Kimio Watanabe
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Kana Okada
Graduate School of Integrated Arts and Sciences, Hiroshima University, 1-7-1 Kagamiyama, Higashi-Hiroshima 739-8521, Japan
Ryoji Fukabori
Department of Molecular Genetics, Institute of Biomedical Sciences, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Yoshimitsu Hayashi
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Koichi Asahi
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Hiroyuki Terawaki
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Kazuto Kobayashi
Department of Molecular Genetics, Institute of Biomedical Sciences, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Tsuyoshi Watanabe
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Masaaki Nakayama
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4–6 months of age) and late phase (7–12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.
