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Since previous experience of stressful situation profoundly affects response to a subsequent novel stressor, we examined changes in gene expression and protein levels of catecholamine biosynthetic enzymes in cardiac ventricles after exposure of chronic psychosocially isolated adult Wistar male rats to short-term immobilization stress. Chronic social isolation did not affect gene expression of tyrosine hydroxylase (TH) in either right or left ventricle. Subsequent immobilization of these animals produced an elevation of TH mRNA level in right and left ventricles. The levels of dopamine-β-hydroxylase (DBH) mRNA were detectable only after immobilization both in right and left ventricles of control and chronically isolated rats. Chronic isolation stress increased phenylethanolamine N-methyltransferase (PNMT) mRNA levels in the right ventricle. Immobilization led to an elevated PNMT mRNA level in right and left ventricles of both control and chronically stressed animals. Protein levels of TH, DBH, and PNMT in right and left ventricles of socially isolated rats were increased after subsequent immobilization. Taking into consideration the role of cardiac catecholamines in physiological and pathophysiological processes, it could be hypothesized that increased catecholamine synthesis in the ventricles after novel immobilization stress could point to the susceptibility of the heart to subsequent stress.

Objective: Social isolation is regarded as one of the most relevant causes of diseases in mammalian species. The activation of the sympathoneural system represents one of the key components of the stress response. The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. The aim of the present study was to determine plasma epinephrine and norepinephrine in individually housed rats, as well as to find out whether splenic gene expression of catecholamine synthesizing enzymes and their protein levels are affected by chronic psychosocial stress. Methods: Tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels were quantified by quantitative real-time RT-PCR. The TH, DBH and PNMT immunoproteins were assayed by Western blot. Results: Chronic social isolation of adult male rats produced a significant increase in plasma catecholamine levels and a decrease in splenic TH mRNA, DBH mRNA and PNMT mRNA. Protein levels of TH, DBH and PNMT were also reduced. Conclusion: These results suggest that increased plasma catecholamines and decreased gene expression and protein levels of catecholamine biosynthetic enzymes in the spleen of chronically individually housed animals might reduce catecholamine synthesis, thus leaving the immunocompetent tissues depleted of catecholamines and consequently leading to an impairment of immune response.

The sympatho-adrenal system represents one of the main systems involved in the response to stressful events because its stress-induced activation results in an increased release of catecholamines. Exercise training acts as an important modulator of sympatho-adrenal system, adrenal medulla and stellate ganglia being two components of this system. This study aimed at investigating physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase in the adrenal medulla and stellate ganglia of chronically psychosocially stressed adult rats exposed daily to 20-min treadmill exercise for 12 weeks, using TaqMan RT-PCR assay. Chronic psychosocial stress decreased gene expression of the examined enzymes in the adrenal medulla and treadmill exercise did not lead to further modulation of the corresponding gene expression. On the other hand, chronic psychosocial stress produced a significant increase of TH (about 51%) and DBH (about 103%) gene expression in stellate ganglia, while treadmill exercise decreased gene expression of these enzymes to control levels in psychosocially stressed rats. Our data indicate that treadmill exercise leads to a decreased gene transcription of catecholamine biosynthetic enzymes in stellate ganglia and attenuation of cardiac noradrenaline production in stressful situations. Reduction of catecholamine synthesis in stellate ganglia may be linked to the beneficial effects of treadmill exercise on cardiovascular system in stressed animals.

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