[article]
| Titre : |
Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice |
| Type de document : |
Texte imprimé et/ou numérique |
| Auteurs : |
David HO-TIENG, Auteur ; Kevin C LISTER, Auteur ; Weihua CAI, Auteur ; Calvin WONG, Auteur ; Nicole BROWN, Auteur ; Jonathan FAN, Auteur ; Volodya HOVHANNISYAN, Auteur ; Sonali UTTAM, Auteur ; Masha PRAGER-KHOUTORSKY, Auteur ; Nahum SONENBERG, Auteur ; Christos G GKOGKAS, Auteur ; Arkady KHOUTORSKY, Auteur |
| Article en page(s) : |
17 |
| Langues : |
Anglais (eng) |
| Mots-clés : |
Animals Microglia/metabolism/pathology Fragile X Mental Retardation Protein/genetics/metabolism Female Male Down-Regulation Behavior, Animal Mice Mice, Inbred C57BL Fragile X Syndrome/metabolism/genetics/pathology Social Behavior Animals, Newborn Fmr1 Animal models Behaviours reminiscent of autism Microglia Council on Animal Care guidelines and approved by McGill University?s Animal Care Committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Fragile X syndrome is caused by the loss of the Fmr1 gene expression. Deletion of Fmr1 in various neuronal and non-neuronal subpopulations in the brain of mice leads to cell-type-specific effects. Microglia, immune cells critical for the refinement of neuronal circuits during brain development, have been implicated in various neurodevelopmental disorders, including fragile X syndrome. However, it is unknown whether reduced Fmr1 expression in microglia leads to molecular and behavioral phenotypes. METHODS: We downregulated Fmr1 in microglia during early and late postnatal development and studied the effect on microglial morphology and distinct behaviours. RESULTS: Female, but not male, adult mice with downregulation of Fmr1 in microglia during early development exhibited reactive microglia and behavioral phenotypes, including enhanced self-grooming and alterations in social interaction. Downregulation of Fmr1 in microglia during late development induced a milder phenotype, characterized by impaired preference for social novelty without affecting microglia morphology. CONCLUSIONS: The downregulation of Fmr1 and its encoded protein FMRP in microglia contributes to behavioural phenotypes in a sex-specific manner. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-025-00648-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 |
in Molecular Autism > 16 (2025) . - 17
[article] Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice [Texte imprimé et/ou numérique] / David HO-TIENG, Auteur ; Kevin C LISTER, Auteur ; Weihua CAI, Auteur ; Calvin WONG, Auteur ; Nicole BROWN, Auteur ; Jonathan FAN, Auteur ; Volodya HOVHANNISYAN, Auteur ; Sonali UTTAM, Auteur ; Masha PRAGER-KHOUTORSKY, Auteur ; Nahum SONENBERG, Auteur ; Christos G GKOGKAS, Auteur ; Arkady KHOUTORSKY, Auteur . - 17. Langues : Anglais ( eng) in Molecular Autism > 16 (2025) . - 17
| Mots-clés : |
Animals Microglia/metabolism/pathology Fragile X Mental Retardation Protein/genetics/metabolism Female Male Down-Regulation Behavior, Animal Mice Mice, Inbred C57BL Fragile X Syndrome/metabolism/genetics/pathology Social Behavior Animals, Newborn Fmr1 Animal models Behaviours reminiscent of autism Microglia Council on Animal Care guidelines and approved by McGill University?s Animal Care Committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Fragile X syndrome is caused by the loss of the Fmr1 gene expression. Deletion of Fmr1 in various neuronal and non-neuronal subpopulations in the brain of mice leads to cell-type-specific effects. Microglia, immune cells critical for the refinement of neuronal circuits during brain development, have been implicated in various neurodevelopmental disorders, including fragile X syndrome. However, it is unknown whether reduced Fmr1 expression in microglia leads to molecular and behavioral phenotypes. METHODS: We downregulated Fmr1 in microglia during early and late postnatal development and studied the effect on microglial morphology and distinct behaviours. RESULTS: Female, but not male, adult mice with downregulation of Fmr1 in microglia during early development exhibited reactive microglia and behavioral phenotypes, including enhanced self-grooming and alterations in social interaction. Downregulation of Fmr1 in microglia during late development induced a milder phenotype, characterized by impaired preference for social novelty without affecting microglia morphology. CONCLUSIONS: The downregulation of Fmr1 and its encoded protein FMRP in microglia contributes to behavioural phenotypes in a sex-specific manner. |
| En ligne : |
https://dx.doi.org/10.1186/s13229-025-00648-2 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 |
|
Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice in Molecular Autism, 16 (2025)
