Early environmental enrichment rescues memory impairments provoked by mild neonatal hypoxia-ischemia in adolescent mice

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  • Rodrigo Orso, Pontificia Universidade Catolica do Rio Grande do Sul
  • ,
  • Kerstin Camile Creutzberg, Pontificia Universidade Catolica do Rio Grande do Sul
  • ,
  • Francisco Sindermann Lumertz, Pontificia Universidade Catolica do Rio Grande do Sul
  • ,
  • Luis Eduardo Wearick-Silva, Pontificia Universidade Catolica do Rio Grande do Sul
  • ,
  • Eduardo Farias Sanches, Universidade Federal do Rio Grande do Sul
  • ,
  • Regis Gemerasca Mestriner, Pontificia Universidade Catolica do Rio Grande do Sul
  • ,
  • Gregers Wegener
  • Rodrigo Grassi-Oliveira

Hypoxia-ischemia (HI) is a consequence of a lack of oxygen and glucose support to the developing brain, which causes several neurodevelopmental impairments. Environmental enrichment (EE) is considered an option to recover the alterations observed in rodents exposed to HI. The aim of this study was to investigate the impact of early EE on memory, hippocampal volume and brain-derived neurotrophic factor (Bbnf) and glucocorticoid receptor (Nr3c1) gene expression of mice exposed to HI. At P10, pups underwent right carotid artery permanent occlusion followed by 35 min of 8% O2 hypoxic environment. Starting at P11, animals were reared in EE or in standard cage (HI-SC or SHAM-SC) conditions until behavioral testing (P45). SHAM pups did not undergo carotid ligation and hypoxic exposure. Memory performance was assessed in the Y-maze, Novel object recognition, and Barnes maze. Animals were then sacrificed for analysis of hippocampal volume and Bdnf and Nr3c1 gene expression. We observed that animals exposed to HI performed worse in all three tests compared to SHAM animals. Furthermore, HI animals exposed to EE did not differ from SHAM animals in all tasks. Moreover, HI decreased hippocampal volume, while animals reared in early EE were not different compared to SHAM animals. Animals exposed to HI also showed upregulated hippocampal Bdnf expression compared to SHAM animals. We conclude that early EE from P11 to P45 proved to be effective in recovering memory impairments and hippocampal volume loss elicited by HI. Nevertheless, Bdnf expression was not associated with the improvements in memory performance observed in animals exposed to EE after a hypoxic-ischemic event.

Original languageEnglish
Article number113237
JournalBehavioural Brain Research
Number of pages11
Publication statusPublished - Jun 2021

Bibliographical note

Funding Information:
This work was supported by the Brazilian funding agencies: Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [grant numbers: 442776/2018-7 , 307130/2018-5 ] and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.

Publisher Copyright:
© 2021 Elsevier B.V.

Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • BDNF, Environmental enrichment, Hippocampus, Hypoxia-Ischemia, Memory

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