FEDERICA CORDELLA

Dottoressa di ricerca

ciclo: XXXIV


supervisore: Silvia Di Angelantonio
relatore: Silvia Di Angelantonio

Titolo della tesi: Antibiotics Treatment Modulates Microglia–Synapses Interaction

‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, birth delivery, altered diet, stress, and antibiotics (ABX) treatment has been recently linked to pathological alteration of brain function and behaviour. Moreover, gut microbiota composition constantly controls microglia maturation, as revealed by morphological observations and gene expression analysis. However, it is unclear whether microglia functional properties and crosstalk with neurons, known to shape and modulate synaptic development and function, are influenced by the gut microbiota. Here, we investigated how antibiotic-mediated alteration of the gut microbiota influences microglial, astrocytic and neuronal functions in adult mice hippocampus. Hippocampal microglia from adult mice treated with oral antibiotics exhibited increased microglia density, altered basal patrolling activity, and impaired process rearrangement in response to damage. Moreover, astrocytes derived from ABX-treated mice displayed an increased density and C3 reactivity, even if in the absence of neuroinflammatory process. Patch clamp recordings at CA3-CA1 synapses revealed that antibiotics treatment alters neuronal functions, reducing spontaneous postsynaptic glutamatergic currents and decreasing synaptic connectivity, without reducing dendritic spines density. Antibiotics treatment was unable to modulate synaptic function in CX3CR1-deficient mice, pointing to an involvement of microglia–neuron crosstalk through the CX3CL1/CX3CR1 axis in the effect of dysbiosis on neuronal functions. Real time PCR analysis of metabolic genes revealed a significant increase in metabolic-gene related expression in hippocampal samples derived from antibiotic-treated mice compared to control. In addition we found out a reduced expression of lipid droplets (LDs) in both microglia and astrocytes derived from ABX-treated mice. Together, our findings show that antibiotic alteration of gut microbiota impairs microglia functionality, thus altering synaptic efficacy, astrocytes homeostasis and altered lipid metabolism, highlighting that CX3CL1/CX3CR1 signalling supports microglia as a major player in the gut–brain axis, and in particular in the gut microbiota-to-neuron communication pathway.

Produzione scientifica

  • 11573/1685183 - 2023 - Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders (01a Articolo in rivista)
    D'ANTONI, CHIARA; MAUTONE, LORENZA; SANCHINI, CATERINA; TONDO, LUCREZIA; GRASSMANN, GRETA; BEZZI, PAOLA; CORDELLA, FEDERICA; DI ANGELANTONIO, SILVIA
  • 11573/1426014 - 2020 - Retinal and brain organoids: bridging the gap between in vivo physiology and in vitro micro-physiology for the study of Alzheimer’s diseases (01g Articolo di rassegna (Review))
    BRIGHI, CARLO; CORDELLA, FEDERICA; DI ANGELANTONIO, SILVIA
  • 11573/1532744 - 2021 - Systemic delivery of a specific antibody targeting the pathological N-terminal truncated tau peptide reduces retinal degeneration in a mouse model of Alzheimer’s Disease (01a Articolo in rivista)
    CORDELLA, FEDERICA; DI ANGELANTONIO, SILVIA
  • 11573/1549009 - 2021 - Novel fragile X syndrome 2D and 3D brain models based on human isogenic FMRP-KO iPSCs (01a Articolo in rivista)
    SALARIS, FEDERICO; CORDELLA, FEDERICA; GHIRGA, SILVIA; ROSITO, MARIA; D'ANTONI, CHIARA; ROSA, ALESSANDRO; DI ANGELANTONIO, SILVIA
  • 11573/1582798 - 2021 - Antibiotics treatment modulates microglia–synapses interaction (01a Articolo in rivista)
    CORDELLA, FEDERICA; SANCHINI, CATERINA; ROSITO, MARIA; FERRUCCI, LAURA; PEDICONI, NATALIA; CORTESE, BARBARA; ANTONANGELI, FABRIZIO; PERUZZI, GIOVANNA; BASILICO, BERNADETTE; PAGANI, FRANCESCA; GRIMALDI, ALFONSO; D'ALESSANDRO, GIUSEPPINA; LIMATOLA, CRISTINA; RAGOZZINO, DAVIDE ANTONIO; DI ANGELANTONIO, SILVIA
  • 11573/1661240 - 2022 - Human iPSC-Derived Cortical Neurons Display Homeostatic Plasticity (01a Articolo in rivista)
    CORDELLA, FEDERICA; FERRUCCI, LAURA; D'ANTONI, CHIARA; GHIRGA, SILVIA; BRIGHI, CARLO; RAGOZZINO, DAVIDE ANTONIO; BEZZI, PAOLA; DI ANGELANTONIO, SILVIA
  • 11573/1565955 - 2022 - Stem cell-based 3D brain organoids for mimicking, investigating, and challenging Alzheimer's diseases (01f Lettera, Nota)
    CORDELLA, FEDERICA; BRIGHI, CARLO; DI ANGELANTONIO, SILVIA
  • 11573/1660557 - 2022 - Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells (01a Articolo in rivista)
    BASILICO, BERNADETTE; LAURO, CLOTILDE; ROSITO, MARIA; GRIECO, MADDALENA; RATANO, PATRIZIA; CORDELLA, FEDERICA; SANCHINI, CATERINA; DI ANGELANTONIO, SILVIA; RAGOZZINO, DAVIDE ANTONIO; CORTESE, BARBARA

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