TY - JOUR
T1 - Effect of uremic toxins on hippocampal cell damage
T2 - analysis in vitro and in rat model of chronic kidney disease
AU - Watanabe, Kimio
AU - Sato, Emiko
AU - Mishima, Eikan
AU - Watanabe, Mayu
AU - Abe, Takaaki
AU - Takahashi, Nobuyuki
AU - Nakayama, Masaaki
N1 - Funding Information:
This work was supported by JSPS KAKENHI [Grant Numbers 15K19461 , 19K08669 ], JSPS KAKENHI [Grant Number 23591196 ] and JADP [Grant Number 2013-1 ].
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Cerebro-renal interaction
KW - Chronic kidney disease
KW - Cognitive impairment
KW - Uremic toxins
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U2 - 10.1016/j.heliyon.2021.e06221
DO - 10.1016/j.heliyon.2021.e06221
M3 - Article
AN - SCOPUS:85100665709
SN - 2405-8440
VL - 7
JO - Heliyon
JF - Heliyon
IS - 2
M1 - e06221
ER -