Abstract
Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.
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Acknowledgements
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 466763/2014-0] and by a generous private donation from Suzana and Carlos Melzer to the USP Bipolar Disorder Research Program (PROMAN). We would like to thank the families of the subjects that donated the brains and provided all information. Camila Nascimento was supported by a post-doctoral scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2017/07089-8].
Funding
This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [grant number 466763/2014-0] and by a generous private donation from Suzana and Carlos Melzer to the USP Bipolar Disorder Research Program (PROMAN). Camila Nascimento was supported by a post-doctoral scholarship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2017/07089-8].
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All the authors contributed to the study conception and design. Experiment conduction, material preparation, data collection and analysis were performed by CN. PVN was responsible for the diagnostic of the bipolar disorder subjects and HK contributed with experiment conduction and analysis. The first draft of the manuscript was written by CN and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.
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Nascimento, C., Nunes, P.V., Kim, H.K. et al. Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study. J Neural Transm 129, 95–103 (2022). https://doi.org/10.1007/s00702-021-02455-4
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DOI: https://doi.org/10.1007/s00702-021-02455-4