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Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet–Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease
Blaine E. Weiss, John C. Gant, Ruei‐Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata et al.. Journal of Neuroscience, 2025-08-15
Topic: Brain proteins, microglia and lab models
While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in response to air puff stimulation of contralateral whiskers) and concurrent calcium transients across astrocyte compartments were reduced in 5xFAD mice relative to WTs. Synchronous activity within multicell astrocyte networks was also impaired in the 5xFAD group. Using a custom application to assess functional coupling between astrocyte end feet and immediately adjacent arteriole segments, we detected deficits in calcium response probability in 5xFAD mice. Moreover, end feet calcium transients following arteriole dilations exhibited a slower onset, reduced amplitude, and lacked relative proportionality to vasomotive activity compared with WTs. The results reveal nuanced alterations in 5xFAD reactive astrocytes highlighted by impaired signaling fidelity between astrocyte end feet and cerebral arterioles. The results have important implications for the mechanistic underpinnings of brain hypometabolism and the disruption of neurophysiologic communication found in AD and other neurodegenerative conditions.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Weiss, B. E., Gant, J. C., Lin, R., Gollihue, J. L., Rogers, C. B., Kraner, S. D., et al. (2025). Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet–Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease. Journal of Neuroscience. https://doi.org/10.1523/jneurosci.0349-25.2025
Vancouver
Weiss BE, Gant JC, Lin R, Gollihue JL, Rogers CB, Kraner SD, et al. Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet–Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease. Journal of Neuroscience. 2025. doi:10.1523/jneurosci.0349-25.2025. PMID: 40816764.
BibTeX
@article{weiss2025-40816764,
author = {Weiss, Blaine E. and Gant, John C. and Lin, Ruei‐Lung and Gollihue, Jenna L. and Rogers, Colin B. and Kraner, Susan D. and Rucker, Edmund B. and Katsumata, Yuriko and others},
title = {{Disrupted Calcium Dynamics in Reactive Astrocytes Occur with End Feet–Arteriole Decoupling in an Amyloid Mouse Model of Alzheimer's Disease}},
journal = {Journal of Neuroscience},
year = {2025},
doi = {10.1523/jneurosci.0349-25.2025},
pmid = {40816764},
url = {https://doi.org/10.1523/jneurosci.0349-25.2025}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Moreover, end feet calcium transients following arteriole dilations exhibited a slower onset, reduced amplitude, and lacked relative proportionality to vasomotive activity compared with WTs.
- The results reveal nuanced alterations in 5xFAD reactive astrocytes highlighted by impaired signaling fidelity between astrocyte end feet and cerebral arterioles.
- The results have important implications for the mechanistic underpinnings of brain hypometabolism and the disruption of neurophysiologic communication found in AD and other neurodegenerative conditions.
Why it matters
In an amyloid mouse model, calcium signaling in reactive astrocytes was disrupted and their communication with small blood vessels was impaired. This is a mouse study of brain signaling, so it does not yet show a treatment or prevention for Alzheimer's disease in people.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Christopher Mark Norris: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Kentucky: institution h-index 824 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40816764) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.0349-25.2025
- PubMed: 40816764
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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Also tagged “mice”
1,150 studies in the library carry the topic tag “mice”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.