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

Autor(es):Mostrar menos -

Degaspari, Sabrina ^[1] ; Tzanno-Martins, Carmen Branco ^[2] ; Fujihara, Clarice Kazue ^[3] ; Zatz, Roberto ^{[3, 2]} ; Branco-Martins, Joao Paulo ^[2] ; Viel, Tania Araujo ^[4] ; Buck, Hudson de Souza ^[5] ; Marques Orellana, Ana Maria ^[1] ; Boehmer, Ana Elisa ^[1] ; Lima, Larissa de Sa ^[1] ; Andreotti, Diana Zukas ^[1] ; Munhoz, Carolina Demarchi ^[1] ; Scavone, Cristoforo ^[1] ; Kawamoto, Elisa Mitiko ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharmacol, Mol Neuropharmacol Lab, Inst Biomed Sci, Sao Paulo - Brazil

^[2] Ctr Integrado Nefrol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Div Renal, Dept Clin Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil

^[5] Santa Casa Sao Paulo Med Sch, Dept Physiol Sci, BR-01221020 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 5 MAY 11 2015.
• Citações Web of Science: 21

Resumo

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-kappa 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-kappa B binding activity and tumor necrosis factor-alpha (TNF-alpha) 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-alpha / 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-kappa B, TNF-alpha and KLOTHO signaling may contribute to Nx-induced CI in rats. (AU)

• Processo FAPESP: 11/50596-1 - Avaliação do envolvimento da via de sinalização Wnt em linfócitos e das alterações plasmáticas de citocinas e corticóides em pacientes com doenças renal crônica em hemodiálise com déficit cognitivo e em animais submetidos ao modelo de nefrectomia parcial 5/6 e de ingestão de adenina
• Beneficiário: Cristoforo Scavone
• Modalidade de apoio: Auxílio à Pesquisa - Regular