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Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

Molecular Psychiatry volume 11, pages 361–371 (2006)Cite this article

Abstract

Hormonal imbalances are involved in many of the age-related pathologies, as neurodegenerative and psychiatric diseases. Specifically, thyroid state alterations in the adult are related to psychological changes and mood disorders as depression. The dentate gyrus of the hippocampal formation undergoes neurogenesis in adult mammals including humans. Recent evidence suggests that depressive disorders and their treatment are tightly related to the number of newly born neurons in the dentate gyrus. We have studied the effect of thyroid hormones (TH) on hippocampal neurogenesis in adult rats in vivo. A short period of adult-onset hypothyroidism impaired normal neurogenesis in the subgranular zone of the dentate gyrus with a 30% reduction in the number of proliferating cells. Hypothyroidism also reduced the number of newborn neuroblasts and immature neurons (doublecortin (DCX) immunopositive cells) which had a severely hypoplastic dendritic arborization. To correlate these changes with hippocampal function, we subjected the rats to the forced swimming and novel object recognition tests. Hypothyroid rats showed normal memory in object recognition, but displayed abnormal behavior in the forced swimming test, indicating a depressive-like disorder. Chronic treatment of hypothyroid rats with TH not only normalized the abnormal behavior but also restored the number of proliferative and DCX-positive cells, and induced growth of their dendritic trees. Therefore, hypothyroidism induced a reversible depressive-like disorder, which correlated to changes in neurogenesis. Our results indicate that TH are essential for adult hippocampal neurogenesis and suggest that mood disorders related to adult-onset hypothyroidism in humans could be due, in part, to impaired neurogenesis.

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Acknowledgements

We thank Marina Sanz Sancristóbal, Mario Soriano, and Ana Isabel Herrero for their excellent technical help, Carmina Criado for providing facilities to perform the behavioral studies, Laura Barrios for her assistance with the statistical analyses and Javier Perez for the art work. We also thank Gabriela Morreale de Escobar and Francisco Escobar del Rey for helpful discussions and advise in the experimental animal design. This work was supported by Grants BFI2001-2412 and BFU2004-05944 (AG-F), BFI2002-00489 (JB), BFI2003-07524 (CV) from the Ministry of Science and Technology and FIS, Instituto de Salud Carlos III, Red de Centros RCMN (C03/08). AM-P and IF-L are the recipients of a fellowship and AG-F and CV of a contract from the Ramón y Cajal Program, all of the Ministry of Science and Technology, Spain.

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  1. Department of Molecular Endocrinology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain

    A Montero-Pedrazuela, R Lavado-Autric, I Fernández-Lamo, J Bernal & A Guadaño-Ferraz

  2. Department of Psychobiology, Universidad Nacional de Educación a Distancia, Madrid, Spain

    C Venero

  3. Laboratorio de Morfologia Celular, Unidad Mixta CIPF-UVEG, Valencia, Spain

    J M García-Verdugo

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  1. A Montero-Pedrazuela
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Correspondence to A Guadaño-Ferraz.

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Montero-Pedrazuela, A., Venero, C., Lavado-Autric, R. et al. Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior. Mol Psychiatry 11, 361–371 (2006). https://doi.org/10.1038/sj.mp.4001802

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