A5057102319- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Genetics and Neurodevelopmental Disorders
- Cellular Mechanics and Interactions
- Gut microbiota and health
- Ubiquitin and proteasome pathways
- Neurological Disease Mechanisms and Treatments
- Adenosine and Purinergic Signaling
- Tryptophan and brain disorders
- Microtubule and mitosis dynamics
- Tissue Engineering and Regenerative Medicine
- Barrier Structure and Function Studies
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- Electrohydrodynamics and Fluid Dynamics
- Stress Responses and Cortisol
- Click Chemistry and Applications
- Hippo pathway signaling and YAP/TAZ
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
Istituto Pasteur
2021-2024
Italian Institute of Technology
2023-2024
Sapienza University of Rome
2017-2023
Institute of Science and Technology Austria
2020-2022
Deficient neuron-microglia signaling during brain development is associated with abnormal synaptic maturation. However, the precise impact of deficient microglia function on maturation and mechanisms involved remain poorly defined. Here we report that mice defective in neuron-to-microglia via fractalkine receptor (Cx3cr1 KO) show reduced microglial branching altered motility develop widespread deficits glutamatergic neurotransmission. We characterized functional properties CA3-CA1 synapses...
Abstract Microglia cells are active players in regulating synaptic development and plasticity the brain. However, how they influence normal functioning of synapses is largely unknown. In this study, we characterized effects pharmacological microglia depletion, achieved by administration PLX5622, on hippocampal CA3‐CA1 adult wild type mice. Following microglial observed a reduction spontaneous evoked glutamatergic activity associated with decrease dendritic spine density. We also appearance...
Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries behavior. Inspired by discovery mutations SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead autism, we employed metabolomic profiling study states cerebral cortex across different developmental stages. We found forebrain undergoes significant remodeling throughout development,...
In glioma, microglia and infiltrating macrophages are exposed to factors that force them produce cytokines chemokines, which contribute tumor growth maintaining a pro-tumorigenic, immunosuppressed microenvironment. We demonstrate housing glioma-bearing mice in enriched environment (EE) reverts the immunosuppressive phenotype of myeloid cells, by modulating inflammatory gene expression. Under these conditions, branching patrolling activity cells is increased, their phagocytic promoted....
De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). In mouse, constitutive Cul3 haploinsufficiency leads motor coordination deficits as well ASD-relevant social and cognitive impairments. However, induction later life does not behaviors, pointing an important role during a critical developmental window. Here we show that is essential regulate neuronal migration and, therefore, heterozygous mutant mice display...
‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked pathological alteration brain function behavior. Moreover, microbiota composition constantly controls microglia maturation, revealed by morphological observations gene expression analysis. However, it is unclear whether functional properties crosstalk with neurons, known shape modulate synaptic development function, are influenced...
Abstract The mature mammalian brain connectome emerges during development via the extension and pruning of neuronal connections. Glial cells have been identified as key players in phagocytic elimination synapses projections. Recently, phosphatidylserine has “eat‐me” signal that guides unnecessary input sources, but associated transduction systems involved such are yet to be described. Here, we Xk‐related protein 8 (Xkr8), a phospholipid scramblase, factor for axons developing brain. We found...
Microglia cells, resident immune cells of the brain, survey brain parenchyma by dynamically extending and retracting their processes. Cl- channels, activated in cellular response to stretch/swelling, take part several functions deeply connected with microglia physiology, including cell shape changes, proliferation, differentiation migration. However, molecular identity functional properties these channels are largely unknown. We investigated swelling-activated currents microglial from acute...
Abstract Complement signaling is thought to serve as an opsonization signal promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated retino-thalamic system, it remains unclear whether complement mediates pruning brain more generally. Here we found that mice lacking receptor 3, major microglia receptor, failed show a deficit either or axon elimination developing mouse cortex. Instead, 3 exhibited perinatal neurons cortex,...
The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by mechanical rigidity their surroundings. epithelial-mesenchymal transition (EMT) is a well-recognized driving force invasive behavior cancer. However, primary mechanisms EMT initiation progression remain unclear. We have previously showed certain substrate stiffness can selectively stimulate human GBM U251-MG GL15 lines motility....
Microglia are the resident immune cells of central nervous system (CNS).In last year, improvements in transgenic mouse technologies and imaging techniques have shed light on microglia functions under physiological conditions.Microglia continuously scan brain parenchyma with their highly motile processes, maintaining tissue homeostasis participating neuronal circuits refinement.Here, we describe a protocol that enables us to perform time-lapse microglial acute hippocampal slices, making image...
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It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding role regulation derived from studies acute brain slices. However, it still uncertain to what extent preparation and maintenance slices can influence microglial whether changes may affect transmission. In this study, we examined impact slice resting time on hippocampal CA1 microglia, by assessing morphological functional parameters at two distinct...
Cells respond dynamically to multiple cues in complex microenvironments, which influence their behaviour, function, and molecular pathways. Despite recent advances, understanding cell interactions such environments remains challenging. While biophysical...
ABSTRACT Microglial cells are active players in regulating synaptic development and plasticity the brain. However, how these influence normal functioning of synapses is largely unknown. In this study, we characterized effects pharmacological depletion microglia, achieved by administration PLX5622, on hippocampal CA3-CA1 adult wild type mice. Following microglial depletion, observed a reduction spontaneous evoked glutamatergic activity associated with decrease dendritic spine density. We also...
Abstract De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 ( CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models evaluate consequences vivo. Our results show that haploinsufficient mice exhibit deficits motor coordination as well ASD-relevant social and cognitive impairments. mutant brain displays cortical lamination abnormalities due defective neuronal migration reduced numbers excitatory inhibitory neurons. In line with observed...
Abstract Complement signaling is thought to serve as an opsonization signal promote the phagocytosis of synapses by microglia. However, while its role in synaptic remodeling has been demonstrated retino-thalamic system, it remains unclear whether complement mediates pruning brain more generally. Here we show that mice lacking 3 receptor ( C3r ), major microglia receptor, fail a deficit either or axon elimination developing mouse cortex. Instead, perinatal neurons, both retina well cortex,...
SUMMARY Surprisingly little is known about the critical metabolic changes that neural cells have to undergo during development and how even mild, temporary shifts in this program can influence brain circuitries behavior. Inspired by discovery mutations SLC7A5 , a transporter of metabolically-relevant large neutral amino acids, lead form autism spectrum disorder, we employed metabolomic profiling study states cerebral cortex across different stages life. We found undergoes significant...
De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models evaluate consequences vivo. Our results show that haploinsufficient mice exhibit deficits motor coordination as well ASD-relevant social and cognitive impairments. mutant brains display cortical lamination abnormalities due defective neuronal migration reduced numbers excitatory inhibitory neurons. In line with observed abnormal...
‘Dysbiosis’ of the adult gut microbiota, in response to challenges such as infection, altered diet, stress, and antibiotics treatment has been recently linked pathological alteration brain func-tion behavior. Moreover, microbiota composition constantly controls microglia matura-tion revealed by morphological observations gene expression analysis. However, it is un-clear whether influences functional properties crosstalk with neu-rons, known shape modulate synaptic...