Repeated Restraint Stress Decreases Na,K-ATPase Activity via Oxidative and Nitrosative Damage in the Frontal Cortex of Rats

Author(s)

Novaes, Leonardo Santana ^[1] ; dos Santos, Nilton Barreto ^[1] ; Dragunas, Guilherme ^[1] ; Perfetto, Juliano Genaro ^[1] ; Carlos Leza, Juan ^[2] ; Scavone, Cristoforo ^[1] ; Munhoz, Carolina Demarchi ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Prestes 1524, Room 323, BR-05508000 Sao Paulo - Brazil

^[2] Univ Complutense Madrid, Fac Med, Ctr Invest Biomed Red Salud Mental CIBERSAM, Dept Pharmacol, Inst Invest Sanitaria, Hosp 12 Octu, Madrid - Spain

• Document type: Journal article
• Source: Neuroscience; v. 393, p. 273-283, NOV 21 2018.
• Web of Science Citations: 5

Abstract

Chronic psychogenic stress can increase neuronal calcium influx and generate the intracellular accumulation of oxidative (ROS) and nitrosative (RNS) reactive species, disrupting synaptic transmission in the brain. These molecules impair the Na,K-ATPase (NKA) activity, whose malfunction has been related to neuropsychiatric disorders, including anxiety, depression, schizophrenia, and neurodegenerative diseases. In this study, we assessed how 14 days of restraint stress in rats affect NKA activity via oxidative/nitrosative damage in the frontal cortex (FCx), a crucial region for emotional and cognitive control. One day after the last stress session (S14 + 1d), but not immediately after the last stress session (S14), alpha 2,3-NKA activity was significantly reduced in the FCx, without changes in the protein levels. The S14 + 1d animals also showed increased lipid peroxidation, iNOS, and AP-1 activities, as well as TNF-alpha protein levels, evidencing oxidative stress and neuroinflammation. No cellular death or neurodegeneration was observed in the FCx of S14 + 1d animals. Pharmacological inhibition of iNOS or COX-2 before each stress session prevented lipid peroxidation and the alpha 2,3-NKA activity loss. Our results show that repeated restraint exposure for 14 days decreases the activity of alpha 2,3-NKA in FCx 24 h after the last stress, an effect associated with augmented inflammatory response and oxidative and nitrosative damage and suggest new pathophysiological roles to neuroinflammation in neuropsychiatric diseases. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 12/24002-0 - Effects of environmental enrichment in long-lasting anxiety symptoms triggered by acute stress: implications in the emotional memory acquisition
• Grantee: Leonardo Santana Novaes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/24727-4 - Comparison of the therapeutical effects of dexamethasone (a synthetic glucocorticoid analogue), and G1 (a G-coupled estrogen receptor, GPER agonist) on the EAE-induced neuroinflammation
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/13843-8 - Protection conferred by environmental enrichment on stress-induced anxiety: the importance of GR, ERK, and CREB pathways in the rat basolateral amygdala
• Grantee: Leonardo Santana Novaes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/03572-3 - The relationship between glucocorticoid receptor activation and the neuronal hyperexcitability in the basolateral amygdala in the restraint stress-induced long-lasting anxiety and their implications in the impaired contextual fear extinction
• Grantee: Carolina Demarchi Munhoz
• Support Opportunities: Regular Research Grants