Effects of exercise training on behavior and brain function after high dose isoproterenol-induced cardiac damage

Abstract

Acute sympathetic stress can result in cardiac fibrosis, but may also lead to mental dysfunction. Exercise training after isoproterenol (ISO)-induced acute sympathetic stress was investigated regarding cardiac damage, neuroinflammation, brain function and behavior. Male Wistar rats (12 months) received ISO or saline. One week later, treadmill running or control handling (sedentary) started. After 4 weeks, cognitive- and exploratory behavior were evaluated, and heart and brain tissues were analyzed regarding cardiac damage, hippocampal neuroinflammation and neuronal function. ISO did not affect cognitive performance nor hippocampal function. However, ISO reduced anxiety, coinciding with locally reduced microglia (processes) size in the hippocampus. Exercise in ISO rats reversed anxiety, did not affect microglia morphology, but increased brain function. Thus, exercise after ISO did not affect cardiac damage, cognition or hippocampal neuroinflammation, but normalized anxiety. Increased localized BDNF expression may indicate improved brain function.

Sex dimorphism in isoproterenol-induced cardiac damage associated neuroinflammation and behavior in old rats

“…In the present study, only old rats have been included, hampering direct comparison with younger ones to establish an age effect. For the latter we have to rely on comparing present results to those obtained in our studies in adult 12 months old male (Toth et al, 2021) and female rats (under review for publication), showing that ISO caused significant cardiac damage in both male and female rats. Although in the 12 months old male rats, microglia morphology suggested ISO-induced hippocampal neuroinflammation, BDNF expression was not affected, and OF behavior even suggested lower anxious/depressive-like behavior, suggesting interaction between the time courses of age-related and ISO-related processes.…”

“…Male (n = 21) and female rats (n = 22) were randomly divided into two groups regarding type of intervention. ISO groups (11 males and 12 females) received 70 mg/kg isoproterenol dissolved in 1 ml/kg saline, control groups (10 males and 10 females) were given 1 ml/kg saline (Toth et al, 2021). Although usually a higher dosage of ISO is used, 85-100 mg/kg, the 70 mg/kg dose was chosen to balance reliable studying effects of ISO and bias because of too high mortality (Toth et al, 2021).…”

“…ISO groups (11 males and 12 females) received 70 mg/kg isoproterenol dissolved in 1 ml/kg saline, control groups (10 males and 10 females) were given 1 ml/kg saline (Toth et al, 2021). Although usually a higher dosage of ISO is used, 85-100 mg/kg, the 70 mg/kg dose was chosen to balance reliable studying effects of ISO and bias because of too high mortality (Toth et al, 2021). Substances were administered on two consecutive days with 24 h in between via subcutaneous injection (Ravindran et al, 2020).…”

“…Effects on cognitive performance were tested using the short-term memory test of object and location. The two memory tests were combined in one protocol (Toth et al, 2021) and took place in a black box of 45 * 55 * 50 cm. The animal was placed in the box and stayed there for the whole test procedure.…”

“…Comparison with results from our studies in 10. 3389/fnagi.2022.854811 12 months old rats (Toth et al, 2021) may indicate interaction between ISO-induced effects and age-related processes. Although selected carefully, effects were studied at single time points, limiting the overview of time courses of these ongoing processes.…”