Tau deletion enhances neurogenesis in adult MAPT‐/‐ mice: Molecular and cell biology/tau. (7th December 2020) - Criado‐Marrero, Marangelie
Abstract: Background: Tau is the major microtubule associated protein (MAPT) that, under normal conditions, supports neuronal microtubule's stability. However, pathological tau self‐aggregates and disrupts microtubules function contributing to common hallmarks in neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal dementia (FTD). Besides dementia, tau pathology has been associated with the progressive development of behavioral symptoms because it affects brain regions in the limbic system and there are comorbid symptoms of depression with AD. However, it is not known if this is a direct consequence of neuropathological changes or a response to the psychological burden of dementia. Methods: The current study investigated the effect of tau deletion in depressive‐like behavior and neurogenesis using the Mapt ‐/‐ mouse model, which contains a targeted deletion of tau gene. We used behavioral (forced swim, tail suspension, learned helplessness) tests and molecular (cell culture, immunohistochemistry and proteomic mass spectrometry) tools to evaluate tau‐induced changes. Results: At 6‐months of age, we found that both female and male Mapt ‐/‐ mice are resistant to depressive behaviors. Unlike depressed patients, the hypothalamic pituitary adrenal axis was not affected in Mapt‐/‐ mice suggesting that the glucocorticoid signaling is not responsible for conferring protection from depression in these mice. 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 tau deletion promotes long‐lasting effects in hippocampal neurogenesis as observed at 14‐months‐old mice. Induction of proteins involved in neurogenesis was observed in limbic areas including the hippocampus, frontal cortex and amygdala of the Mapt ‐/‐ mice. Conclusion: 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.