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Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II.
Exp Gerontol. 2017 01; 87(Pt A):108-112.EG

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Electronic address: mitsuyam@gpo.kumamoto-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27916702

Citation

Nakagawa, Takashi, et al. "Chronic Kidney Disease Accelerates Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Through Angiotensin II." Experimental Gerontology, vol. 87, no. Pt A, 2017, pp. 108-112.
Nakagawa T, Hasegawa Y, Uekawa K, et al. Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II. Exp Gerontol. 2017;87(Pt A):108-112.
Nakagawa, T., Hasegawa, Y., Uekawa, K., & Kim-Mitsuyama, S. (2017). Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II. Experimental Gerontology, 87(Pt A), 108-112. https://doi.org/10.1016/j.exger.2016.11.012
Nakagawa T, et al. Chronic Kidney Disease Accelerates Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Through Angiotensin II. Exp Gerontol. 2017;87(Pt A):108-112. PubMed PMID: 27916702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II. AU - Nakagawa,Takashi, AU - Hasegawa,Yu, AU - Uekawa,Ken, AU - Kim-Mitsuyama,Shokei, Y1 - 2016/12/01/ PY - 2016/09/06/received PY - 2016/11/10/revised PY - 2016/11/28/accepted PY - 2016/12/6/pubmed PY - 2017/10/17/medline PY - 2016/12/6/entrez KW - Aging KW - Alzheimer's disease KW - Angiotensin KW - Blood-brain barrier KW - CKD SP - 108 EP - 112 JF - Experimental gerontology JO - Exp Gerontol VL - 87 IS - Pt A N2 - 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. SN - 1873-6815 UR - https://www.unboundmedicine.com/medline/citation/27916702/Chronic_kidney_disease_accelerates_cognitive_impairment_in_a_mouse_model_of_Alzheimer's_disease_through_angiotensin_II_ DB - PRIME DP - Unbound Medicine ER -