Minute- and second-scale hippocampal network dysfunctions in the 3xTgAD mouse model of Alzheimer's disease are prevented by TSPO knockout
Vidal, B.; Badina, A. M.; Dorogan, V.; Schirmbeck, G.; Sanches, E. F.; Ceyzeriat, K.; Knoop, M.; Abjean, L.; Tsartsalis, S.; Sizonenko, S.; Baud, O.; Millet, P.; Zerbi, V.; Tournier, B. B.
Show abstract
The 18kDa translocator protein (TSPO) is widely recognized as a biomarker of neuroinflammation, but recent evidence suggests that it may also play a direct role in the pathophysiology of neurological conditions with an inflammatory component such as Alzheimers disease (AD). In this study, we leveraged functional ultrasound imaging (fUSi) to assess how TSPO knockout influences brain activity and connectivity in the 3xTgAD mouse model of AD. Resting-state scans were performed in 16-month-old male and female mice across four genotypes: WT, TSPO-/-, 3xTgAD or 3xTgAD.TSPO-/-. Using a data-driven approach, we identified key functional networks, including a bilateral hippocampal-amygdala limbic network. Dual regression analysis revealed increased engagement of the ventral hippocampus within the limbic network and elevated hemodynamic variance in 3xTgAD mice compared to WT. Moreover, co-activation patterns (CAPs) analysis showed abnormal activation/deactivation cycles involving the dorsal hippocampus, both of which were prevented by TSPO knockout without affecting amyloid or tau burden. Our findings highlight a functional role for TSPO in shaping network dynamics and suggest that its deletion can mitigate brain dysfunction in AD models.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease 96%
- Functional network collapse in neurodegenerative disease 96%
- Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer 95%
Similar papers in this journal
- Functional dynamic network connectivity differentiates biological patterns in the Alzheimer's disease continuum 94%
- Regional interneuron transcriptional changes reveal pathologic markers of disease progression in a mouse model of Alzheimer's disease 92%
- The Caribbean-Hispanic Alzheimer's Brain Transcriptome Reveals Ancestry-Specific Disease Mechanisms 92%
Similar papers in this journal
- Selective vulnerability and resilience to Alzheimer's disease tauopathy as a function of genes and the connectome 96%
- Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy 94%
- Default mode network tau predicts future clinical decline in atypical early Alzheimer’s disease 94%
Similar papers in this journal
- Detecting the effect of genetic diversity on brain composition in an Alzheimer's disease mouse model 95%
- Multimodal identification of the mouse brain using simultaneous Ca2+ imaging and fMRI 94%
- Knockout of the longevity gene Klotho perturbs aging- and Alzheimer's disease-linked brain microRNAs and tRNA fragments 94%
Similar papers in this journal
- Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's Disease 94%
- Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system 94%
- Applying high-resolution spatial transcriptomics to characterise the amyloid plaque cell niche in Alzheimer's Disease 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.