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Synergistic and additive effects of enriched environment and lithium on the generation of new cells in adult mouse hippocampus

  • Translational Neurosciences - Original Article
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Abstract

Hippocampal atrophy is reported in several neuropathological disorders. The hippocampal dentate gyrus (DG) is a brain region where adult neurogenesis constitutively occurs. There are some reports suggesting the ability of endogenous neurogenesis to initiate neuronal repair in the hippocampus in response to neuropathological conditions, but its capacity to compensate for neuronal loss is limited. Among strategies to enhance adult hippocampal neurogenesis are enriched environment and lithium. This study aimed to assess whether both strategies could interact to potentiate the generation of new cells in the adult DG. Healthy adult male C57BL/6 mice were divided into four treatment groups for 28 days: control, lithium, enriched environment, enriched environment plus lithium. The animals were injected with BrdU (cell proliferation marker) shortly before the start of the treatments and killed 28 days later for analysis of newly generated cells. Two-way ANOVA followed by post hoc test revealed a significant synergistic interaction between enriched environment and lithium in the total number of BrdU+ cells in the entire DG (p = 0.019), a trend towards significant synergistic interaction in the dorsal DG (p = 0.075), and a significant additive effect in the ventral DG (p = 0.001). These findings indicate that the combination of enriched environment and lithium has both synergistic and additive effects on the generation of new cells in the healthy adult DG (these effects being possibly segregated along the dorso-ventral axis of the hippocampus), and suggest that it might be worth investigating whether this combination would have a similar effect in neuropathological conditions.

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Acknowledgments

This study was funded by the State of Sao Paulo Research Support Foundation (FAPESP; Projects 2009/52825-8, 2009/53008-3, 2011/23039-4, 2011/24022-8). The Laboratory of Neuroscience LIM-27 receives financial support from the Alzira Denise Hertzog Silva Benevolent Association (ABADHS). The authors thank the Center for Research Support (CEAPESQ) of the Institute of Psychiatry for statistical assistance.

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The authors declare no conflict of interest related to the present study.

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  1. Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos 785, São Paulo, SP, 05403-010, Brazil

    Evelin L. Schaeffer, Fabiana G. Cerulli, Hélio O. X. Souza & Wagner F. Gattaz

  2. Lipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Clinical Hospital, Faculty of Medicine, University of Sao Paulo, Av. Dr. Arnaldo 455, São Paulo, SP, 01246-000, Brazil

    Sergio Catanozi

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  1. Evelin L. Schaeffer
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Correspondence to Evelin L. Schaeffer.

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Schaeffer, E.L., Cerulli, F.G., Souza, H.O.X. et al. Synergistic and additive effects of enriched environment and lithium on the generation of new cells in adult mouse hippocampus. J Neural Transm 121, 695–706 (2014). https://doi.org/10.1007/s00702-014-1175-5

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