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Subtle Alterations in Hippocampal Neuronal Activity Coincide With Early Sex‐Specific Differences in Amyloidosis and Microglia in a Pre‐Symptomatic Mouse Model of Alzheimer‐Like Pathology
Thomas Chaigneau, Sha Sha, Candice M. Roux, Saba Aïd, Alice Faucher, Yannick Chantran, Guillaume Dorothée, Slavica Krantic. Glia, 2025-04-30
Topic: Brain proteins, microglia and lab models
Growing evidence highlights sex-related differences in the pathogenesis of Alzheimer's disease (AD). Yet, early impact of sex on neuronal activity and microglia in the hippocampus, a main site of memory formation and one of the most vulnerable brain areas in AD, remains poorly understood. We thus assessed these issues by using APPPS1 mouse model of AD-like amyloid pathology at a pre-symptomatic stage (5-6 months). Our electrophysiological data point to opposite alterations in hippocampal CA1 neurons' basal glutamatergic neurotransmission and response to excitatory inputs between male and female APPPS1 mice. These complex changes in neuronal activity are likely to precede plasticity impairments, which do not yet translate into sexual dimorphism of Long-Term Potentiation (LTP) at the studied age. Alteration in synaptic transmission in males coincides with an increased number and coverage of microglia, together with increased plaque coverage, as compared to the female hippocampus. Such increased microgliosis in males is accompanied by complex sex-related differences in the expression of specific transcriptomic markers Disease-Associated Microglia (DAM)/Microglial neurodegenerative phenotype (MGnD), whereas homeostatic (M0) markers were unaffected. Our data show for the first time that subtle alterations in hippocampal neuronal activity coincide with early sex-related differences in amyloidosis and microglia already at the pre-symptomatic stage of AD-like pathology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Chaigneau, T., Sha, S., Roux, C. M., Aïd, S., Faucher, A., Chantran, Y., et al. (2025). Subtle Alterations in Hippocampal Neuronal Activity Coincide With Early Sex‐Specific Differences in Amyloidosis and Microglia in a Pre‐Symptomatic Mouse Model of Alzheimer‐Like Pathology. Glia. https://doi.org/10.1002/glia.70029
Vancouver
Chaigneau T, Sha S, Roux CM, Aïd S, Faucher A, Chantran Y, et al. Subtle Alterations in Hippocampal Neuronal Activity Coincide With Early Sex‐Specific Differences in Amyloidosis and Microglia in a Pre‐Symptomatic Mouse Model of Alzheimer‐Like Pathology. Glia. 2025. doi:10.1002/glia.70029. PMID: 40304030.
BibTeX
@article{chaigneau2025-40304030,
author = {Chaigneau, Thomas and Sha, Sha and Roux, Candice M. and Aïd, Saba and Faucher, Alice and Chantran, Yannick and Dorothée, Guillaume and Krantic, Slavica},
title = {{Subtle Alterations in Hippocampal Neuronal Activity Coincide With Early Sex‐Specific Differences in Amyloidosis and Microglia in a Pre‐Symptomatic Mouse Model of Alzheimer‐Like Pathology}},
journal = {Glia},
year = {2025},
doi = {10.1002/glia.70029},
pmid = {40304030},
url = {https://doi.org/10.1002/glia.70029}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Alteration in synaptic transmission in males coincides with an increased number and coverage of microglia, together with increased plaque coverage, as compared to the female hippocampus.
Why it matters
In a mouse model of Alzheimer's-like pathology before symptoms appeared, male and female mice showed opposite changes in hippocampal neuronal activity, and males had more microglia and plaque coverage. These early animal findings point to sex differences in the disease process but do not yet indicate a treatment.
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 (Glia) |
| Journal's citation record | 2 / 4 | Glia: journal h-index 233 (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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.6× 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 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Slavica M Krantic: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40304030) |
| Free to read | 2 / 2 | Free to read |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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