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Enriched environment induces beneficial effects on memory deficits and microglial activation in the hippocampus of type 1 diabetic rats

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Abstract

Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic–pituitary–adrenal axis and microglial activation in diabetic animals.

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Acknowledgments

The authors would like to thank the members of Laboratory of Comparative Histophysiology, the Electron Microscopy Center of the Federal University of Rio Grande do Sul for the microscopy analyzes and Henrique B. Biehl for his technical assistance. The authors are also grateful for the financial support provided by CNPq, CAPES, FAPERGS 10/0304-2, UFRGS and Matilde Achaval, MD, PhD, CNPq1A researcher.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP: 90050-170, Porto Alegre, RS, Brazil

    Francele Valente Piazza, Lígia Aline Centenaro, Patrícia Severo do Nascimento, Matilde Achaval & Simone Marcuzzo

  2. Laboratório de Histofisiologia Comparada, Departamento de Ciências Morfológicas, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP: 90050-170, Porto Alegre, RS, Brazil

    Francele Valente Piazza, Ethiane Segabinazi, Lígia Aline Centenaro, Patrícia Severo do Nascimento, Matilde Achaval & Simone Marcuzzo

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  1. Francele Valente Piazza
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  2. Ethiane Segabinazi
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  3. Lígia Aline Centenaro
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Correspondence to Simone Marcuzzo.

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Piazza, F.V., Segabinazi, E., Centenaro, L.A. et al. Enriched environment induces beneficial effects on memory deficits and microglial activation in the hippocampus of type 1 diabetic rats. Metab Brain Dis 29, 93–104 (2014). https://doi.org/10.1007/s11011-013-9467-2

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