Impact of brain redox biomarkers on the emotional and cognitive-related states in male and female adolescent rats: A descriptive analysis

Abstract

Redox imbalance can affect several processes within the brain (e.g., synaptic plasticity, neurotransmitters release and their related pathways), leading to altered emotional and cognitive states. These effects can be particularly detrimental during adolescence, a critical period for brain development when some of the brain areas regulating emotional and cognitive functions, such as prefrontal cortex (PFC) and hippocampus (HIPP), are not fully matured yet. Nonetheless, the role of redox markers in the modulation of emotional and cognitive states in adolescent rodents remains under-investigated. Here, we performed correlation analyses between behavior and biomolecular data of redox markers measured in PFC and HIPP of male and female adolescent naïve rats, together with the evaluation of possible sex differences. Our results reveal sex differences in anxiety-like behavior as well as exploratory activity in the open field test, and in fear memory in the auditory fear conditioning task. Moreover, female rats showed decreased NADPH oxidase 2 (NOX-2) and catalase protein levels in PFC, alongside reduced nuclear factor erythroid 2-related factor 2 (NRF-2) and increased lipid peroxidation content in HIPP, thus highlighting sex differences in these redox markers. When considering both sexes together, NRF-2 and NOX-2 expression in PFC and HIPP correlated with several emotional- and cognitive-related behavioral parameters, suggesting that redox status might affect brain maturation, and thus behavior, during adolescence. Collectively, these findings point towards a possible role of redox-related markers in the occurrence of emotional and cognitive behaviors, providing new insights into their potential as pharmacological targets for the treatment of psychiatric disorders.

Keywords: Adolescence; Anxiety; Central nervous system; Cognition; Oxidative stress.