The effects of exercise training on heart, brain and behavior, in the isoproterenol-induced cardiac infarct model in middle-aged female rats

Tóth, Kata; Oroszi, Tamás; Zee, Eddy A. van der; Nyakas, Csaba; Schoemaker, Regien G.

doi:10.1038/s41598-022-14168-z

Cited by 2 publications

(11 citation statements)

References 55 publications

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“…On the other hand, since ISO was dosed based on body weight, female rats with significantly lower body weights and higher relative heart (ns) and brain weights, could have received too less ISO to cause an effect. However, in our previous studies in 12 months old male (Toth et al, 2021) and female rats (Toth et al, 2022), using the same dose per body weight as used in the present study, led to a significant and similar magnitude of cardiac damage and reduced cardiac function in both sexes.…”

Section: Limitationssupporting

confidence: 52%

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

Tóth

Oroszi²,

Zee³

et al. 2022

Front. Aging Neurosci.

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Acute cardiac damage can be induced by isoproterenol injections in animals. The associated inflammatory response could be reflected in the brain as neuroinflammation, with potential consequences for brain function and behavior. Although cardiac responses are reported age and sex-related, for neuroinflammation and brain function this is virtually unknown. Therefore, cardiac damage and its consequences for neuroinflammation, brain function and behavior were compared in aged male and female rats. Wistar rats of 24 months of age were treated with isoproterenol (ISO, twice s.c.) or saline. Four weeks after injections, exploratory behavior and short-term memory were tested. Then, rats were sacrificed. Hearts were collected to measure cardiac damage. Brain tissue was collected to obtain measures of neuroinflammation and brain function. In male-, but not in female rats, ISO induced significant cardiac damage. Accordingly, mortality was higher in males than in females. Baseline hippocampal microglia activity was lower in females, while ISO induced neuroinflammation in both sexes, Hippocampal brain-derived neurotrophic factor expression appeared lower in females, without effects of ISO. In the open field test, ISO-treated males, but not females, displayed anxiety-like behavior. No effects of ISO were observed on short-term memory in either sex. In conclusion, sex dimorphism in effects of ISO was observed for cardiac damage and open field behavior. However, these effects could not be related to differences in hippocampal neuroinflammation or neuronal function.

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Section: Limitationssupporting

confidence: 52%

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

Tóth

Oroszi²,

Zee³

et al. 2022

Front. Aging Neurosci.

Self Cite

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show abstract

“…Although we anticipated cardiac damage-induced anxiety/depressive-like behavior in the ISO-treated rats (Tkachenko et al, 2018;Hu et al, 2020), in agreement with our previous study on middle-aged female rats (Toth et al, 2022a), ISO with and without exercise training had no effect on behavior in the OF. Similarly, at 24 months of age, no effect of ISO was observed in OF behavior in female rats, but anxiety-associated effects were seen in male rats (Toth et al, 2022b).…”

Section: E Ects On Behavior Depression/anxietysupporting

confidence: 91%

“…As anticipated from our previous study in female rats (Toth et al, 2022a), ISO increased cardiac collagen levels. Although exercise by itself may slightly increase cardiac collagen in salinetreated rats, potentially by increasing fibroblast growth factor 21 (Ma et al, 2021), the ISO-induced cardiac fibrosis was completely reversed.…”

Section: E Ects On the Heartsupporting

confidence: 88%

“…Based on the literature, WBV may affect neuroinflammation in female rats (Raval et al, 2018) as well as in male rats (Oroszi et al, 2022a). However, neither in male (Toth et al, 2021) nor in female rats (Toth et al, 2022a), exercise affected microglia activity after ISO. In the present study, overall hippocampal microglia activity was neither affected by ISO, nor by the interventions.…”

Section: Neuroinflammationmentioning

confidence: 99%

“…However, we are well aware that this provides a model for the consequences of cardiac damage, rather than its etiology of it. To compare the effects of WBV to exercise after ISO, the exercise protocol was based on our previous studies in male and female rats (Toth et al, 2021(Toth et al, , 2022a and the WBV protocol on our exposure time response pilot. Cardiac function measurements in the female rat study suggested a reduced cardiac performance after exercise, which may suggest a too-severe exercise protocol for these females.…”

Section: Limitationsmentioning

confidence: 99%

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Whole-body vibration as a passive alternative to exercise after myocardial damage in middle-aged female rats: Effects on the heart, the brain, and behavior

Tóth

Oroszi²,

Nyakas³

et al. 2023

Front. Aging Neurosci.

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BackgroundFemales with cardiovascular disease seem more vulnerable to develop concomitant mental problems, such as depression and cognitive decline. Although exercise is shown beneficial in cardiovascular disease as well as in mental functions, these patients may be incapable or unmotivated to perform exercise. Whole body vibration (WBV) could provide a passive alternative to exercise. Aim of the present study was to compare WBV to exercise after isoproterenol (ISO)-induced myocardial damage in female rats, regarding effects on heart, brain and behavior.MethodsOne week after ISO (70 mg/kg s.c., on 2 consecutive days) or saline injections, 12 months old female rats were assigned to WBV (10 minutes daily), treadmill running (30 minutes daily) or pseudo intervention for 5 weeks. During the last 10 days, behavioral tests were performed regarding depressive-like behavior, cognitive function, and motor performance. Rats were sacrificed, brains and hearts were dissected for (immuno)histochemistry.ResultsSignificant ISO-induced cardiac collagen deposition (0.67 ± 0.10 vs 0.18 ± 0.03%) was absent after running (0.45 ± 0.26 vs 0.46 ± 0.08%), but not after WBV (0.83 ± 0.12 vs 0.41 ± 0.05%). However, WBV as well as running significantly reduced hippocampal (CA3) collagen content in ISO-treated rats. Significant regional differences in hippocampal microglia activity and brain derived neurotrophic factor (BDNF) expression were observed. Significant ISO-induced CA1 microglia activation was reduced after WBV as well as running, while opposite effects were observed in the CA3; significant reduction after ISO that was restored by WBV and running. Both WBV and running reversed the ISO-induced increased BDNF expression in the CA1, Dentate gyrus and Hilus, but not in the CA3 area. Whereas running had no significant effect on behavior in the ISO-treated rats, WBV may be associated with short-term spatial memory in the novel location recognition test.ConclusionAlthough the female rats did not show the anticipated depressive-like behavior or cognitive decline after ISO, our data indicated regional effects on neuroinflammation and BDNF expression in the hippocampus, that were merely normalized by both WBV and exercise. Therefore, apart from the potential concern about the lack of cardiac collagen reduction, WBV may provide a relevant alternative for physical exercise.

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The effects of exercise training on heart, brain and behavior, in the isoproterenol-induced cardiac infarct model in middle-aged female rats

Cited by 2 publications

References 55 publications

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

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

Whole-body vibration as a passive alternative to exercise after myocardial damage in middle-aged female rats: Effects on the heart, the brain, and behavior

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