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Open AccessArticle

Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice

Department of Molecular Medicine, USF Health Byrd Institute, University of South Florida, Tampa, FL 33613, USA
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL 33620, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 210; (registering DOI)
Received: 17 December 2019 / Revised: 9 January 2020 / Accepted: 11 January 2020 / Published: 14 January 2020
(This article belongs to the Collection Functions of Nuclear Receptors)
Tau dysfunction is common in several neurodegenerative diseases including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Affective symptoms have often been associated with aberrant tau pathology and are commonly comorbid in patients with tauopathies, indicating a connection between tau functioning and mechanisms of depression. The current study investigated depression-like behavior in Mapt−/− mice, which contain a targeted deletion of the gene coding for tau. We show that 6-month Mapt−/− mice are resistant to depressive behaviors, as evidenced by decreased immobility time in the forced swim and tail suspension tests, as well as increased escape behavior in a learned helplessness task. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5-bromo-2-deoxyuridine (BrdU) labeling. We found that neurogenesis is increased in the dentate gyrus of 14-month-old Mapt−/− brains compared to wild type, providing a potential mechanism for their behavioral phenotypes. In addition to the hippocampus, an upregulation of proteins involved in neurogenesis was observed in the frontal cortex and amygdala of the Mapt−/− mice using proteomic mass spectrometry. All together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression. View Full-Text
Keywords: tauopathies; depression; hippocampal neurogenesis; stress; glucocorticoid receptor; Alzheimer’s disease tauopathies; depression; hippocampal neurogenesis; stress; glucocorticoid receptor; Alzheimer’s disease
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Criado-Marrero, M.; Sabbagh, J.J.; Jones, M.R.; Chaput, D.; Dickey, C.A.; Blair, L.J. Hippocampal Neurogenesis Is Enhanced in Adult Tau Deficient Mice. Cells 2020, 9, 210.

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