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Brain-Derived Neurotrophic Factor Prevents Depressive-Like Behaviors in Early-Symptomatic YAC128 Huntington’s Disease Mice

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Abstract

Huntington disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the Huntington disease gene. The symptomatic stage of the disease is defined by the onset of motor symptoms. However, psychiatric disturbances, including depression, are common features of HD and can occur a decade before the manifestation of motor symptoms. We used the YAC128 transgenic mice (which develop motor deficits at a later stage, allowing more time to study depressive behaviors without the confounding effects of motor impairment) to test the effects of intranasal brain-derived neurotrophic factor (BDNF) treatment for 15 days in the occurrence of depressive-like behaviors. Using multiple well-validated behavioral tests, we found that BDNF treatment alleviated anhedonic and depressive-like behaviors in the YAC128 HD mice. Furthermore, we also investigated whether the antidepressant-like effects of BDNF were associated with an increase in adult hippocampal neurogenesis. However, BDNF treatment only increased cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of wild-type (WT) mice, without altering these parameters in their YAC128 counterparts. Moreover, BDNF treatment did not cause an increase in the number of dendritic branches in the hippocampal DG when compared with animals treated with vehicle. In conclusion, our results suggest that non-invasive administration of BDNF via the intranasal route may have important therapeutic potential for treating mood disturbances in early-symptomatic HD patients.

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Funding

A.R.C., J.G.M., and A.L.S.R. acknowledge funding from the Science Without Borders funding program [Programa Ciência Sem Fronteiras/ Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Project #403120/2012-8] of the Brazilian Federal Government. P.S.B. acknowledges funding from CNPq Project # 480176/2013-2.

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  1. Victor Silva da Fonsêca and André R. da Silva Colla contributed equally to this work.

Authors and Affiliations

  1. Department of Morphological Sciences, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    Victor Silva da Fonsêca, Cristine de Paula Nascimento-Castro, Evelini Plácido & Patricia S. Brocardo

  2. Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil

    André R. da Silva Colla, Julia Macedo Rosa, Marcelo Farina & Ana Lúcia S. Rodrigues

  3. Division of Medical Sciences, UBC Island Medical Program, University of Victoria, Victoria, BC, V8W 2Y2, Canada

    Joana Gil-Mohapel

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  1. Victor Silva da Fonsêca
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da Fonsêca, V.S., da Silva Colla, A.R., de Paula Nascimento-Castro, C. et al. Brain-Derived Neurotrophic Factor Prevents Depressive-Like Behaviors in Early-Symptomatic YAC128 Huntington’s Disease Mice. Mol Neurobiol 55, 7201–7215 (2018). https://doi.org/10.1007/s12035-018-0890-6

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