Microglia are the resident immune cells of the brain and have been implicated in mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by the presence of a supernumerary chromosome 21, which contains genes essential for the function of the immune system. Here, we investigated the presence of microglial alterations and their implication for cognitive impairment in the Dp(16) mouse model of DS. In the hippocampus of Dp(16) mice and individuals with DS, we found microglial morphology indicative of an activated state. Accordingly, we found increased levels of pro-inflammatory cytokines and a phagocytosis marker in Dp(16) mice. In addition, Dp(16) mice showed decreased dendritic spine density and cognitive deficits. Remarkably, depletion of defective microglia by PLX3397 treatment or rescue of the microglia activated state by the commonly used anti-inflammatory drug acetaminophen fully rescued dendritic-spine density and cognitive deficits in Dp(16) mice. Our data suggest an involvement of microglia in the cognitive impairment of DS animals and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS.

Rescuing over-activated microglia by acetominophen treatment restoers cognitive performance in the Dp(16) mouse model of Down Syndrome / Pinto, Bruno Henrique. - (2019 Feb 20).

Rescuing over-activated microglia by acetominophen treatment restoers cognitive performance in the Dp(16) mouse model of Down Syndrome

Pinto, Bruno Henrique
2019

Abstract

Microglia are the resident immune cells of the brain and have been implicated in mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by the presence of a supernumerary chromosome 21, which contains genes essential for the function of the immune system. Here, we investigated the presence of microglial alterations and their implication for cognitive impairment in the Dp(16) mouse model of DS. In the hippocampus of Dp(16) mice and individuals with DS, we found microglial morphology indicative of an activated state. Accordingly, we found increased levels of pro-inflammatory cytokines and a phagocytosis marker in Dp(16) mice. In addition, Dp(16) mice showed decreased dendritic spine density and cognitive deficits. Remarkably, depletion of defective microglia by PLX3397 treatment or rescue of the microglia activated state by the commonly used anti-inflammatory drug acetaminophen fully rescued dendritic-spine density and cognitive deficits in Dp(16) mice. Our data suggest an involvement of microglia in the cognitive impairment of DS animals and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS.
BIO/09 FISIOLOGIA
Scienze biologiche
Biology
brain
central nervous system
chromosome 21
Down syndrome (DS)
microglia
Neuroscience
Scuola Normale Superiore
Cancedda, Laura
Cattaneo, Antonino
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/86007
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