Excessive local host-graft connectivity in aging and amyloid-loaded brain.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
10 Jun 2022
10 Jun 2022
Historique:
entrez:
10
6
2022
pubmed:
11
6
2022
medline:
11
6
2022
Statut:
ppublish
Résumé
Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment on transplant connectivity. To explore the effect of amyloid pathology in Alzheimer's disease (AD) and aging, we examined graft connectivity using monosynaptic rabies virus tracing in APP/PS1 mice and in 16- to 18-month-old wild-type (WT) mice. Transplanted neurons differentiated within 4 weeks and integrated well into the host visual cortex, receiving input from the appropriate brain regions for this area. Unexpectedly, we found a prominent several-fold increase in local inputs, in both amyloid-loaded and aged environments. State-of-the-art deep proteome analysis using mass spectrometry highlights complement system activation as a common denominator of environments promoting excessive local input connectivity. These data therefore reveal the key role of the host pathology in shaping the input connectome, calling for caution in extrapolating results from one pathological condition to another.
Identifiants
pubmed: 35687689
doi: 10.1126/sciadv.abg9287
pmc: PMC9187230
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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