Maternal separation induces changes in TREK-1 and 5HT(1A) expression in brain areas involved in the stress response in a sex-dependent way

Author(s)

Francis-Oliveira, J. ^[1] ; Shieh, I. C. ^[1] ; Vilar Higa, G. S. ^[2] ; Barbosa, M. A. ^[1] ; De Pasquale, R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Biomed Sci Inst 1, Dept Physiol & Biophys, Ave Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Math Computat Cognit Ctr, Neurogenet Lab, Rua Arcturus 03, BR-09606070 Sao Bernardo Do Campo, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 396, JAN 1 2021.
• Web of Science Citations: 0

Abstract

Depression is a prevalent disease in modern society, and has been linked to stressful events at early ages. Women are more susceptible to depression, and the neural basis for this are still under investigation. Serotonin is known to be involved in depression, and a decrease in 5HT(1A) expression is observed on temporal and cortical areas in both men and women with depression. As knockout animals for TREK-1 are resilient to depression, this channel has emerged as a new potential pharmacological target for depression treatment. In this study, maternal separation (MS) was used to emulate early-life stress, and evaluate behaviour, as well as TREK-1 and 5HT(1A) expression in the brain using immunohistochemistry. In juvenile females, 5HT(1A) reduction coupled to increased TREK-1 in the dentate gyrus (DG) was associated with behavioural despair, as well as increased TREK-1 expression in basolateral amygdala (BLA) and prelimbic cortex (PL). In juvenile males, MS induced an increase in 5HT(1A) in the BLA, and in TREK-1 in the PL, while no behavioural despair was observed. Anhedonia and anxiety-like behaviour were not induced by MS. We conclude stress-induced increase in TREK-1 in PL and GD is associated to depression, while 5HT(1A) changes coupled to TREK-1 changes may be necessary to induce depression, with females being more vulnerable to MS effects than males. Thus, TREK-1 and 5HT(1A) may be potential pharmacological targets for antidepressants development. (AU)

• FAPESP's process: 16/09116-0 - Evaluation of TREK-1 physiological role in neural stress modulation
• Grantee: José Francis de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/23874-0 - Oxidative stress and synaptic plasticity in primary visual cortex
• Grantee: Roberto De Pasquale
• Support Opportunities: Research Grants - Young Investigators Grants