Glial activation is moderated by sex in response to amyloidosis but not to tau pathology in mouse models of neurodegenerative diseases.
Amyloid
Microglia
Sex
TSPO
Tau
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
14 Dec 2020
14 Dec 2020
Historique:
received:
20
07
2020
accepted:
25
11
2020
entrez:
15
12
2020
pubmed:
16
12
2020
medline:
1
10
2021
Statut:
epublish
Résumé
In vivo assessment of neuroinflammation by 18-kDa translocator protein positron-emission-tomography (TSPO-PET) ligands receives growing interest in preclinical and clinical research of neurodegenerative disorders. Higher TSPO-PET binding as a surrogate for microglial activation in females has been reported for cognitively normal humans, but such effects have not yet been evaluated in rodent models of neurodegeneration and their controls. Thus, we aimed to investigate the impact of sex on microglial activation in amyloid and tau mouse models and wild-type controls. TSPO-PET ( Wild-type mice showed an increased TSPO-PET signal over time (female +23%, male +4%), with a significant sex × age interaction (T = - 4.171, p < 0.001). The Aβ model App Female mice indicate sex-dependent microglia activation in aging and in response to amyloidosis but not in response to tau pathology. This calls for consideration of sex difference in TSPO-PET studies of microglial activation in mouse models of neurodegeneration and by extension in human studies.
Sections du résumé
BACKGROUND
BACKGROUND
In vivo assessment of neuroinflammation by 18-kDa translocator protein positron-emission-tomography (TSPO-PET) ligands receives growing interest in preclinical and clinical research of neurodegenerative disorders. Higher TSPO-PET binding as a surrogate for microglial activation in females has been reported for cognitively normal humans, but such effects have not yet been evaluated in rodent models of neurodegeneration and their controls. Thus, we aimed to investigate the impact of sex on microglial activation in amyloid and tau mouse models and wild-type controls.
METHODS
METHODS
TSPO-PET (
RESULTS
RESULTS
Wild-type mice showed an increased TSPO-PET signal over time (female +23%, male +4%), with a significant sex × age interaction (T = - 4.171, p < 0.001). The Aβ model App
CONCLUSION
CONCLUSIONS
Female mice indicate sex-dependent microglia activation in aging and in response to amyloidosis but not in response to tau pathology. This calls for consideration of sex difference in TSPO-PET studies of microglial activation in mouse models of neurodegeneration and by extension in human studies.
Identifiants
pubmed: 33317543
doi: 10.1186/s12974-020-02046-2
pii: 10.1186/s12974-020-02046-2
pmc: PMC7737385
doi:
Substances chimiques
Mapt protein, mouse
0
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
374Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : BR4580/1-1
Organisme : Deutsche Forschungsgemeinschaft
ID : RO5194/1-1
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC 2145 SyNergy
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