6533b851fe1ef96bd12aa2ac

RESEARCH PRODUCT

Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome.

Laura E. PerliniTiziano CatelaniGiovanni MorelliAmos FumagalliAndrea PetrettoMartina BartolucciAnnalisa SavardiEmilo VareaLaura CanceddaMohit RastogiAndrea ContestabileBruno Pinto

subject

0301 basic medicineAdultMaleDown syndromeDendritic spinemedicine.medical_treatmentAminopyridinesMice TransgenicHippocampal formationHippocampus03 medical and health sciencesMice0302 clinical medicineImmune systemCognitionMedicineHippocampus (mythology)AnimalsHumansPyrrolesNeuroinflammationMicrogliabusiness.industryGeneral NeuroscienceAnti-Inflammatory Agents Non-SteroidalAge Factorsmedicine.disease3. Good healthMice Inbred C57BLDisease Models Animal030104 developmental biologymedicine.anatomical_structureCytokinenervous systemFemaleMicrogliaDown SyndromebusinessNeuroscience030217 neurology & neurosurgery

description

Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals.

yearjournalcountryeditionlanguage
2020-01-15Neuron
10.1016/j.neuron.2020.09.010https://pubmed.ncbi.nlm.nih.gov/33301721