Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs
Open accessAbstract
In the rTg4510 mouse model, expression of the mutant human tau variant P301L leads to development of neurofibrillary tangles (NFTs), neuronal death, and memory impairment, reminiscent of the pathology observed in human tauopathies. In the present study, we examined the effects of mutant tau expression on the electrophysiology and morphology of individual neurons using whole-cell patch-clamp recordings and biocytin filling of pyramidal cells in cortical slices prepared from rTg4510 (TG) and wild-type (WT) littermate mice. Among the TG cells, 42% contained a clear Thioflavin-S positive inclusion in the soma and were categorized as NFT positive (NFT+), while 58% had no discernable inclusion and were categorized as NFT negative (NFT-). The resting membrane potential (V(r)) was significantly depolarized (+8 mV) in TG cells, and as a consequence, evoked repetitive action potential (AP) firing rates were also significantly increased. Further, single APs were significantly shorter in duration in TG cells and the depolarizing voltage deflection or "sag" evoked by hyperpolarization was significantly greater in amplitude. In addition to these functional electrophysiological changes, TG cells exhibited significant morphological alterations, including loss or significant atrophy of the apical tuft, reduced dendritic complexity and length, and reduced spine density. Importantly, NFT- and NFT+ TG cells were indistinguishable with regard to both morphological and electrophysiological properties. Our observations show that expression of mutated tau results in significant structural and functional changes in neurons, but that these changes occur independent of mature NFT formation.
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Expression of mutant tau in mouse models of Alzheimer's disease-like tau neuropathologies can result in a significant loss of dendritic spines and synapses.
“Significantly, the expression of mutant tau in mouse models of Alzheimer’s disease-like tau neuropathologies can result in a significant loss of dendritic spines and synapses (Mocanu et al., 2008; Bittner et al., 2010; Rocher et al., 2010).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Rocher et al., 2010
The Results section ('Significant reduction in dendritic spine density in TG cells'; page unavailable) reports 29% and 38% reductions in spine density in mutant-tau mice. The Discussion ('Dramatic and uniform decrease in spine density in TG cells'; page unavailable) also mentions reduced synaptophysin labeling in another mutant-tau mouse model, but this paper does not establish a significant loss of synapses in its own mice. (LLM, conf=0.85)
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- Authors
- Rocher, A. B., Crimins, J. L., Amatrudo, J. M., Kinson, M. S., Todd-Brown, M. A., Lewis, J., & Luebke, J. I.
- Affiliations
- Boston University (US)
- Mayo Clinic (US)
- Corresponding author
- Luebke, J.I.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 223
- Issue
- 2
- Pages
- 385-393
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC2864360
- OpenAlex
- W2124538980
- Cited by
- 187
- References
- 5
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 13 · 2020: 17 · 2019: 7 · 2018: 9 · 2017: 14 · 2016: 9 · 2015: 17 · 2014: 10 · 2013: 12 · 2012: 14
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P30 AG13846, R01 AG025062)
- National Institute of Neurological Disorders and Stroke (R01 NS046355)
- Alzheimer's Association (IIRG-06-27277)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- P301L tau, neurofibrillary tangles, tauopathy, neuronal electrophysiology, resting membrane potential, action potential firing rate, dendritic morphology, dendritic spine density, cortical pyramidal neurons
- MeSH terms
- Action Potentials, Alzheimer Disease, Animals, Atrophy, Humans, Membrane Potentials, Mice, Transgenic, Organ Culture Techniques, Structure-Activity Relationship, Neurofibrillary Tangles, tau Proteins, Point Mutation, Pyramidal Cells, Patch-Clamp Techniques, Tauopathies, Dendritic Spines, Mice
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