Dataset Information

Extracellular vesicles are crucial mediators in orchestrating brain development and disease

ABSTRACT: Extracellular vesicles have been the center of many studies focusing on neuron-to-neuron communication while the role of EVs in progenitor-to-neuron and -astrocyte communication occurring during brain development has not been systematically investigated. In this project, we focus on the physiological characterization, dynamic and function of human EVs during human brain development using human-derived cerebral organoids, neural progenitors, neurons and astrocytes. We examined the composition and function of EVs, in patients with myoclonic epilepsy and find alterations in size, composition and function. This study sheds new light on the biology of EVs during brain development.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebral Cortex Neuron, Astrocyte Of The Cerebral Cortex, Cell Culture, Neural Progenitor Cell

DISEASE(S): Progressive Myoclonus Epilepsy 1a

SUBMITTER: Giuseppina Maccarrone

LAB HEAD: Silvia Cappello

PROVIDER: PXD028438 | Pride | 2023-07-20

REPOSITORIES: Pride

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Publications

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles.

Pipicelli Fabrizia F Baumann Natalia N Di Giaimo Rossella R Forero-Echeverry Andrea A Kyrousi Christina C Bonrath Rebecca R Maccarrone Giuseppina G Jabaudon Denis D Cappello Silvia S

Science advances 20230519 20

Disruption in neurogenesis and neuronal migration can influence the assembly of cortical circuits, affecting the excitatory-inhibitory balance and resulting in neurodevelopmental and neuropsychiatric disorders. Using ventral cerebral organoids and dorsoventral cerebral assembloids with mutations in the extracellular matrix gene <i>LGALS3BP</i>, we show that extracellular vesicles released into the extracellular environment regulate the molecular differentiation of neurons, resulting in alteratio ...[more]

PMID: 37205765

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Project description:Morphine, a commonly used antinociceptive drug in hospitals, is known to cross the blood-brain barrier (BBB) by first passing through brain endothelial cells. Despite its pain-relieving effect, morphine also has detrimental effects, such as the potential induction of redox imbalance in the brain. However, there is still insufficient evidence of these effects on the brain, particularly on the brain endothelial cells and the extracellular vesicles that they naturally release. Indeed, extracellular vesicles (EVs) are nanosized bioparticles produced by almost all cell types and are currently thought to reflect the physiological state of their parent cells. These vesicles have emerged as a promising source of biomarkers by indicating the functional or dys-functional state of their parent cells and, thus, allowing a better understanding of the biological processes involved in an adverse state. However, there is very little information on the mor-phine effect on human brain microvascular endothelial cells (HBMECs), and even less on their released EVs. Therefore, the current study aimed at unraveling the detrimental mechanisms of morphine exposure (at 1, 10, 25, 50 and 100 µM) for 24 h on human brain microvascular endothe-lial cells as well as on their associated EVs. Isolation of EVs was carried out using an affini-ty-based method. Several orthogonal techniques (NTA, western blotting and proteomics analy-sis) were used to validate the EVs enrichment, quality and concentration. Data-independent mass spectrometry (DIA-MS)-based proteomics was applied in order to analyze the proteome modu-lations induced by morphine on HBMECs and EVs. We were able to quantify almost 5500 pro-teins in HBMECs and 1500 proteins in EVs, of which 256 and 148, respectively, were found to be differentially expressed in at least one condition. Pathway enrichment analysis revealed that the “cell adhesion and extracellular matrix remodeling” process and the “HIF1 pathway”, a pathway related to oxidative stress responses, were significantly modulated upon morphine exposure in HBMECs and EVs. Altogether, the combination of proteomics and bioinformatics findings high-lighted shared pathways between HBMECs exposed to morphine and their released EVs. These results put forward molecular signatures of morphine-induced toxicity in HBMECs that were also carried by EVs. Therefore, EVs could potentially be regarded as a useful tool to investigate brain endothelial cells dysfunction, and to a different extent, the BBB dysfunction in patient cir-culation using these “signature pathways”.

Dataset Information

Extracellular vesicles are crucial mediators in orchestrating brain development and disease

Publications

Non-cell-autonomous regulation of interneuron specification mediated by extracellular vesicles.

Similar Datasets

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