Kidney failure can trigger neural inflammation

Kidney failure can trigger neural inflammation

For some time it is known that chronic renal failure, or progressive loss of kidney ability to filter the blood – a condition that affects one in 10 people in Brazil – may in some cases lead to the development of cognitive complications like depression, loss of memory and dementia. Now, in a study published in the journal PLoS One, a group of Brazilian researchers have identified the mechanisms involved in this process. In experiments with animal models coordinated by pharmacologist Cristoforo Scavone, of the Molecular Neuropharmacology Laboratory at the Institute of Biomedical Sciences, University of São Paulo (ICB-USP), they found that impaired renal function triggers neural inflammation that can affect brain function.

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

Evaluation of the involvement of WNT signaling pathway in lymphocytes and plasma cytokine changes and corticosteroids in patients with chronic kidney disease on hemodialysis with and without cognitive impairment and in animals subjected to the pair nephrectomy model.

(FAPESP Process No. 2011 / 50596-1) – Modality Research Assistance – Regular;

Responsible researcher: Cristoforo Scavone.

Scientific article
Degaspari, S. et al. Altered KLOTHO NF-kB and TNF-α-Signaling Are Correlated with Cognitive Impairment Nephrectomy-Induced in Rats. PLoS One. May 2015.