Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II

Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairmen...

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Bibliographic Details
Published in:Experimental gerontology 2017-01, Vol.87 (Pt A), p.108-112
Main Authors: Nakagawa, Takashi, Hasegawa, Yu, Uekawa, Ken, Kim-Mitsuyama, Shokei
Format: Article
Language:English
Subjects:
Aging
Aging - drug effects
Alzheimer Disease - complications
Alzheimer's disease
Angiotensin
Angiotensin II Type 1 Receptor Blockers - administration & dosage
Animals
Blood-brain barrier
Blood-Brain Barrier - metabolism
CKD
Cognition - drug effects
Cognitive Dysfunction - drug therapy
Cognitive Dysfunction - etiology
Disease Models, Animal
Hippocampus - metabolism
Imidazoles - administration & dosage
Maze Learning - drug effects
Memory - drug effects
Mice
Mice, Transgenic
Oxidative Stress - drug effects
Renal Insufficiency, Chronic - complications
Tetrazoles - administration & dosage
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Summary:Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding an adenine-containing diet and the effect on cognitive function was compared between both strains. There was no significant difference regarding the severity of CKD induced by adenine between the strains. In 5XFAD mice, the CKD group exhibited significant cognitive impairment while the control group (control diet-fed group) did not, as evidenced by a passive avoidance test. On the other hand, in wild-type mice, neither the CKD group nor the control group showed cognitive impairment. Thus, CKD itself appears to accelerate cognitive impairment in AD mice. (2) We also examined the effect of olmesartan, an angiotensin II receptor blocker, on 5XFAD mice with CKD to elucidate the potential involvement of angiotensin II. As evidenced by the findings of the water maze test, olmesartan treatment significantly ameliorated the impairment of spatial learning and memory function induced by CKD in 5XFAD mice. Olmesartan treatment significantly ameliorated blood-brain barrier (BBB) disruption induced by CKD in 5XFAD mice. Furthermore, olmesartan reduced hippocampal oxidative stress in 5XFAD with CKD to similar levels to the control group of 5XFAD fed standard diet. Hence, the amelioration of CKD-induced cognitive impairment in 5XFAD mice by olmesartan appears to be mediated by the suppression of BBB disruption or oxidative stress. In conclusion, we obtained the evidence suggesting that CKD itself accelerates cognitive impairment in AD mice, through angiotensin II. Thus, our work provides a novel insight into the underlying mechanism of the link between CKD and AD. •Chronic kidney disease (CKD) accelerates cognitive impairment in AD mice.•Angiotensin II is involved in CKD-induced cognitive impairment in AD mice.•CKD causes blood brain barrier disruption in AD mice, through angiotensin II.
ISSN:0531-5565
1873-6815
DOI:10.1016/j.exger.2016.11.012