Effect of uremic toxins on hippocampal cell damage: analysis in vitro and in rat model of chronic kidney disease
Kimio Watanabe,
Emiko Sato,
Eikan Mishima,
Mayu Watanabe,
Takaaki Abe,
Nobuyuki Takahashi,
Masaaki Nakayama
Affiliations
Kimio Watanabe
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan; Department of Blood Purification, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan; Division of Kidney Center, St Luke's International Hospital, Tokyo, 104-8560, Japan; Corresponding author.
Emiko Sato
Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, 980-8578, Japan; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan; Corresponding author.
Eikan Mishima
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan
Mayu Watanabe
Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, 980-8578, Japan
Takaaki Abe
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan
Nobuyuki Takahashi
Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, 980-8578, Japan; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan
Masaaki Nakayama
Department of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan; Division of Kidney Center, St Luke's International Hospital, Tokyo, 104-8560, Japan; Research Division of Dialysis Treatment and Chronic Kidney Disease, Tohoku University Hospital, Sendai, 980-8574, Japan
One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats. Among the uremic toxins analyzed, indoxyl sulfate, indole, 3-indoleacetate, and methylglyoxal significantly decreased viability and glutathione level in HT-22 cells. The mixture of these uremic toxins also decreased viability and glutathione level at a lower dose. Adenine-induced CKD rat showed marked renal damage, increased urinary oxidative stress markers, and increased numbers of pyknotic neuronal cells in hippocampus. CKD rats with damaged hippocampus demonstrated poor learning process when tested using the Morris water maze test. Our results suggest that uremic toxins have a toxic effect on hippocampal neuronal cells and uremic CKD rats shows pyknosis in hippocampus.
