Abstract
Rationale
Oxidative stress and neurotrophins are among the most important factors involved in several pathophysiological brain processes. In addition, long-term exposure to stressful situations has deleterious effects on behaviour. We have previously shown that stressed female BALB/c mice show poor learning performance and that this behaviour is reversed by glatiramer acetate (GA) treatment.
Objectives
We investigated the involvement of the hippocampal oxidative status and neurotrophin levels in cognitive deficit and the improvement of this deficit by GA treatment in chronic stressed BALB/c mice.
Methods
Female BALB/c mice were exposed to a chronic mild stress (CMS) model for 9 weeks. During the last 3 weeks of the stress exposure, one group of mice was subcutaneously injected four times with 100 μg GA/mouse. Following this period, behavioural studies were performed. The mice were then sacrificed, and biochemical studies were performed on the hippocampus.
Results
The stressed mice exhibited a significant decline in their performance in the open-field and in object-in-place tasks. This decline was accompanied by an increase in reactive oxygen species (ROS) and a decrease in nitric oxide (NO) production by neuronal nitric oxide synthase (nNOS). Neither antioxidant defences nor neurotrophin protein levels were involved in this process. Interestingly, the administration of GA re-established the normal levels of ROS, restored nNOS activity and improved learning performance.
Conclusions
The GA treatment improved learning and memory in female BALB/c mice under chronic stress through a mechanism that involves the regulation of NO production, which in turn modulates the ROS levels.
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Acknowledgments
The authors thank María Rosa Gonzalez Murano for her technical assistance, Daniel Gonzalez for his valuable help in the animal stress model and Noemí Cappano and Patricia Fernandez for their secretarial assistance. This work was supported by grants from CONICET (PIP 00281) and from the University of Buenos Aires (UBACyT 2002010010633) to AMG.
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The authors declare that there are no conflicts of interest.
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Pascuan, C.G., Simon, E.H., Genaro, A.M. et al. Involvement of nitric oxide in improving stress-induced behavioural alteration by glatiramer acetate treatment in female BALB/c mice. Psychopharmacology 232, 1595–1605 (2015). https://doi.org/10.1007/s00213-014-3791-z
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DOI: https://doi.org/10.1007/s00213-014-3791-z