Dataset Information

Altered KLOTHO and NF-?B-TNF-? Signaling Are Correlated with Nephrectomy-Induced Cognitive Impairment in Rats.

ABSTRACT: Renal insufficiency can have a negative impact on cognitive function. Neuroinflammation and changes in klotho levels associate with chronic kidney disease (CKD) and may play a role in the development of cognitive impairment (CI). The present study evaluates the correlation of cognitive deficits with neuroinflammation and soluble KLOTHO in the cerebral spinal fluid (CSF) and brain tissue of nephrectomized rats (Nx), with 5/6 renal mass ablation. Nx and sham Munich Wistar rats were tested over 4 months for locomotor activity, as well as inhibitory avoidance or novel object recognition, which started 30 days after the surgery. EMSA for Nuclear factor-?B and MILLIPLEXMAP or ELISA kit were used to evaluate cytokines, glucocorticoid and KLOTHO levels. Nx animals that showed a loss in aversive-related memory and attention were included in the CI group (Nx-CI) (n=14) and compared to animals with intact learning (Nx-M n=12 and Sham n=20 groups). CSF and tissue samples were collected 24 hours after the last behavioral test. The results show that the Nx-groups have increased NF-?B binding activity and tumor necrosis factor-alpha (TNF-?) levels in the hippocampus and frontal cortex, with these changes more pronounced in the Nx-CI group frontal cortex. In addition, the Nx-CI group showed significantly increased CSF glucocorticoid levels and TNF-? /IL-10 ratio compared to the Sham group. Klotho levels were decreased in Nx-CI frontal cortex but not in hippocampus, when compared to Nx-M and Sham groups. Overall, these results suggest that neuroinflammation mediated by frontal cortex NF-?B, TNF-? and KLOTHO signaling may contribute to Nx-induced CI in rats.

SUBMITTER: Degaspari S

PROVIDER: S-EPMC4427267 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Altered KLOTHO and NF-κB-TNF-α Signaling Are Correlated with Nephrectomy-Induced Cognitive Impairment in Rats.

Degaspari Sabrina S Tzanno-Martins Carmen Branco CB Fujihara Clarice Kazue CK Zatz Roberto R Branco-Martins João Paulo JP Viel Tania Araujo TA Buck Hudson de Souza Hde S Orellana Ana Maria Marques AM Böhmer Ana Elisa AE Lima Larissa de Sá Lde S Andreotti Diana Zukas DZ Munhoz Carolina Demarchi CD Scavone Cristoforo C Kawamoto Elisa Mitiko EM

PloS one 20150511 5

Renal insufficiency can have a negative impact on cognitive function. Neuroinflammation and changes in klotho levels associate with chronic kidney disease (CKD) and may play a role in the development of cognitive impairment (CI). The present study evaluates the correlation of cognitive deficits with neuroinflammation and soluble KLOTHO in the cerebral spinal fluid (CSF) and brain tissue of nephrectomized rats (Nx), with 5/6 renal mass ablation. Nx and sham Munich Wistar rats were tested over 4 m ...[more]

PMID: 25961830

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Dataset Information

Altered KLOTHO and NF-?B-TNF-? Signaling Are Correlated with Nephrectomy-Induced Cognitive Impairment in Rats.

Publications

Altered KLOTHO and NF-κB-TNF-α Signaling Are Correlated with Nephrectomy-Induced Cognitive Impairment in Rats.

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