Prefrontal Catecholaminergic Turnover and Antioxidant Defense System of Chronically Stressed Rats

Abstract

This study examined the effects of chronic restraint stress (CRS) on gene expression of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), dopamine transporter (DAT), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2), catechol-O-methyltransferase (COMT) and antioxidant enzymes such as superoxide dismutase (SOD1 and SOD2), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), as well as concentrations of dopamine (DA) and noradrenaline (NA), activities of monoamine oxidase (MAO A and MAOB) and activities of antioxidant enzymes (SOD1, SOD2, CAT, GPx and GR) in the rat prefrontal cortex (PFC). We found that CRS decreases gene expression of TH and DBH and concentrations of DA, which probably confirms the decrease of de novo synthesis of catecholamine. CRS increased protein levels of NET and VMAT2, which was followed by increased NA concentration. The increased activity of MAO A and MAO B, as well as increased protein levels of COMT probably indicate increased catecholamine degradation, which was followed by increased activity of SOD1, SOD2 and CAT, as well as decreased activity of GPx under stress conditions. Our findings confirm the increased prefrontal noradrenergic turnover in animals exposed to CRS. The molecular mechanisms by which CRS changes catecholaminergic turnover and the antioxidant defense system in the PFC may be very important for research on numerous psychiatric diseases caused by chronic stress.