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Updated: May 25, 2026

Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
Isolation stress during the prepubertal period in rats induces long-lasting neurochemical changes in the prefrontal
R Krolow1, C Noschang, S N Weis
1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Ramiro Barcelos, 2600 (Anexo) Lab. 37., Porto Alegre, Rio Grande do Sul 90035-003, Brazil.
Insights
Early life social isolation in male rats causes lasting oxidative stress and energy metabolism changes in the prefrontal cortex. A palatable diet did not reverse these long-term effects.
Area of Science:
- Neuroscience
- Developmental Psychology
- Biochemistry
Background:
- Social isolation during early development can induce significant behavioral and neurochemical alterations.
- The prefrontal cortex is particularly vulnerable to developmental changes and stress during this period.
- Palatable diets have shown potential in mitigating some stress-induced effects.
Purpose of the Study:
- To investigate the impact of early-life isolation stress on oxidative stress and energy metabolism in the rat prefrontal cortex.
- To assess if a palatable diet during the prepubertal period can counteract these stress-induced effects.
- To examine these effects in both juvenile and adult male rats.
Main Methods:
- Rats were subjected to social isolation or standard housing during the prepubertal period.
- Some isolated rats had access to a palatable diet.
- Parameters measured included oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase), Na(+),K(+)-ATPase activity, respiratory chain enzyme activities (Complex IV), and mitochondrial function in the prefrontal cortex.
Main Results:
- Isolation stress increased superoxide dismutase and Complex IV activities in juveniles, with effects persisting into adulthood.
- Catalase activity showed an interaction between stress and diet in juveniles, and was reduced by stress in adults.
- Isolation stress decreased Na(+),K(+)-ATPase activity in adult rats, while palatable diet increased it in juveniles (effect reversed upon removal).
Conclusions:
- Prepubertal social isolation induces persistent changes in antioxidant enzymes and energy metabolism within the male rat prefrontal cortex.
- A palatable diet consumed during the prepubertal period was insufficient to reverse the long-lasting detrimental effects of isolation stress.
- These findings highlight the enduring impact of early-life stress on brain function and metabolism.
Abstract:
Social isolation during postnatal development leads to behavioral and neurochemical changes, and a particular susceptibility of the prefrontal cortex to interventions during this period has been suggested. In addition, some studies showed that consumption of a palatable diet reduces some of the stress effects. Therefore, our aim is to investigate the effect of isolation stress in early life on some parameters of oxidative stress and energy metabolism (Na(+),K(+)-ATPase activity, respiratory chain enzymes activities and mitochondrial mass and potential) in prefrontal cortex of juvenile and adult male rats. We also verified if the consumption of a palatable diet during the prepubertal period would reduce stress effects. The results showed that, in juvenile animals, isolation stress increased superoxide dismutase and Complex IV activities and these effects were still observed in the adulthood. An interaction between stress and diet was observed in catalase activity in juveniles, while only the stress effect was detected in adults, reducing catalase activity. Access to a palatable diet increased Na(+),K(+)-ATPase activity in juveniles, an effect that was reversed after removing this diet. On the other hand, isolation stress induced a decreased activity of this enzyme in adulthood. No effects were observed on glutathione peroxidase, total thiols and free radicals production, as well as on mitochondrial mass and potential. In conclusion, isolation stress in the prepubertal period leads to long-lasting changes on antioxidant enzymes and energetic metabolism in the prefrontal cortex of male rats, and a palatable diet was not able to reverse these stress-induced effects.

