Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis
Open accessAbstract
Tau is a microtubule‐associated neuronal protein found mainly in axons. However, its presence in dendrites and dendritic spines is particularly relevant due to its involvement in synaptic plasticity and neurodegeneration. Here, we show that Tau plays a novel in vivo role in the morphological and synaptic maturation of newborn hippocampal granule neurons under basal conditions. Furthermore, we reveal that Tau is involved in the selective cell death of immature granule neurons caused by acute stress. Also, Tau deficiency protects newborn neurons from the stress‐induced dendritic atrophy and loss of postsynaptic densities (PSDs). Strikingly, we also demonstrate that Tau regulates the increase in newborn neuron survival triggered by environmental enrichment (EE). Moreover, newborn granule neurons from Tau−/− mice did not show any stimulatory effect of EE on dendritic development or on PSD generation. Thus, our data demonstrate that Tau−/− mice show impairments in the maturation of newborn granule neurons under basal conditions and that they are insensitive to the modulation of adult hippocampal neurogenesis exerted by both stimulatory and detrimental stimuli. Tau regulates the in vivo maturation of newborn granule neurons under physiological conditions. In addition, Tau deficiency prevents both the detrimental and stimulatory actions of acute stress and environmental enrichment, respectively, on the functional maturation of these cells. Altogether, our data shed light on novel functions of Tau protein related to the plastic modulation of adult hippocampal neurogenesis by external stimuli. Tau protein plays an unexpected key role in the regulation of adult hippocampal neurogenesis, both under basal conditions and in response to stressing or enriching environmental settings.
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Genetic deletion studies indicate that endogenous tau participates in neuronal processes including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity, and DNA/RNA stability.
“Genetic deletion studies indicate that endogenous tau participates in a range of neuronal processes, including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity [10–22], and stability of DNA and RNA stability [23].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [16]
The Introduction describes tau’s role in microtubule stabilization, and the Results report altered synaptic properties in tau-knockout granule neurons. The Discussion also mentions synaptic-plasticity changes, while the References list work on tau-dependent mitochondrial pausing and network hyperexcitability. This paper does not itself establish effects on mitochondrial dynamics or network activity. DNA/RNA stability is attached to a different citation, [23], in the citing sentence. (LLM, conf=0.82)
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- Authors
- Pallas‐Bazarra, N., Jurado‐Arjona, J., Navarrete, M., Esteban, J. A., Hernández, F., Ávila, J., & Llorens‐Martín, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Ávila, Jesús
- ORCID
- Venue
- The EMBO Journal
- Published
- 2016-05-19
- Volume
- 35
- Issue
- 13
- Pages
- 1417-1436
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC4876034
- OpenAlex
- W2402047081
- Cited by
- 101
- References
- 11
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 5 · 2023: 12 · 2022: 13 · 2021: 19 · 2020: 13 · 2019: 9 · 2018: 10 · 2017: 12
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-sa)
- Funders
- Alzheimer's Association New Investigator Research Grant (2015‐NIRG‐340709)
- Ministerio de Economía y Competitividad (SAF‐2014‐5040‐P, BUF2013‐40664‐P, SAF2014‐58598‐JIN, SAF2014‐57233‐R)
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- tau protein, adult hippocampal neurogenesis, dendritic cell maturation, postsynaptic density, acute stress, environmental enrichment, neuronal survival, dendritic atrophy, synapse maturation, dendritic spines
- MeSH terms
- Animals, Hippocampus, tau Proteins, Mice, Knockout, Mice, Neurogenesis
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