Neurological consequences of exercise during prenatal Zika virus exposure to mice pups

Abstract

Purpose/Aim

Zika virus (ZIKV) infection during the pregnancy period is related to microcephaly and neurobehavioral disorders at birth, while prenatal exercise is supposed to provide neuroprotection in newborns pups. The aim of this study was to investigate the neurological consequences of exercise during prenatal ZIKV exposure to mice pups.

Material and methods

Twelve weeks female mice were randomly assigned into three groups: Control group, intraperitoneally injected with saline (Control); untrained group, intraperitoneally injected with ZIKV (ZIKV); and trained group, intraperitoneally injected with ZIKV (ZIKV/swim). There was one familiarization week prior to the beginning of the swimming training. Dams swam for 60 min/session, 5 days/week, during 4 weeks. Mating occurred between the fifth and seventh day of the first week of the swimming training. ZIKV 10⁶ plaque-forming units/100 µl (10⁶ PFUs/100 µl) or an equal volume of saline was intraperitoneally injected in the pregnant mice at embryonic day 10.5. Pup’s body mass and brain weight were measured at postnatal day 1 (P1). Behavioral tests were performed from P30 to P35. Thereafter, hippocampal levels of syntaxin-1, GFAP, IBA-1, and BDNF were measured.

Results

Exercise during prenatal ZIKV exposure prevented brain atrophy, development of depression, anxiety, and disruption of social behavior. Exercise during prenatal ZIKV exposure inhibited the overexpression of microglia (IBA-1) and astrocytes (GFAP), with reduction of BDNF levels in the hippocampi of female and male mice pups. No significant changes were seen in syntaxin-1 levels.

Conclusion

Our findings reveal beneficial effects of exercise during pregnancy exposure to ZIKV in mice pups.

Keywords:

• Swimming
• physical exercise
• inflammation
• anxiety
• depression
• social interaction

Acknowledgments

We thank Coordination for the Improvement of Higher Education Personnel (CAPES)-Brazil. The authors also acknowledge the Integrated Center for Graduate Studies and Health Research (CIPq) from the Federal University of the Jequitinhonha and Mucuri Valleys for providing equipment and technical support for the experiments. Decit/SCTIE/MoH for financial support. Professor Erna Kroon, Virus Laboratory-UFMG, for kindly providing the animals and viral sample.

Authors’ contributions

R.A.L.S., and D.B.O. designed the study. R.A.L.S. and M.F.D.P. wrote the manuscript. R.A.L.S., L.R.S.O., H.S.O., D.A.F., F.A.S. performed the research. R.A.L.S., L.R.S.O., H.S.O., M.F.D.P., R.C.C., and D.B.O. analyzed the data. R.A.L.S., M.F.D.P., E.R-V., R.C.C., D.B.O. contributed the reagents, materials, analysis tools and laboratory facilities. R.A.L.S., L.R.S.O., H.S.O., D.A.F., F.A.S., H.R.L., M.F.D.P., E.R-V., R.C.C., and D.B.O analyzed and discussed the results. R.A.L.S., L.R.S.O., H.S.O., D.A.F., F.A.S., H.R.L., M.F.D.P., E.R-V., R.C.C., and D.B.O revised the manuscript.

Disclosure statement

The authors declare no competing interests.

Ethics approval

Experiments and animal procedures were conducted according to the Principles of Laboratory Animal Care (Brazilian Arouca Law and US National Institutes of Health). This study was approved by the Ethics Committee on Animal Use of the Universidade Federal dos Vales do Jequitinhonha e Mucuri (022/2019).

Additional information

Funding

This study was financed in part by the Coordination for the Improvement of Higher Education Personnel (CAPES)-Finance Code 001.