Thin graphene oxide nanoflakes modulate glutamatergic synapses in the amygdala cultured circuits: Exploiting synaptic approaches to anxiety disorders

Secomandi, Nicola; Biagioni, Audrey Franceschi; Kostarelos, Kostas; Cellot, Giada; Ballerini, Laura

doi:10.1016/j.nano.2020.102174

Cited by 11 publications

(25 citation statements)

References 37 publications

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“…However, if we considered only experiments with low synaptic activity, where glutamatergic and GABAergic events can be easily distinguished by their time course (Fig. S7 ) [ 40 , 41 ], we found—in two experiments with exosomes from a patient—a higher occurrence of glutamatergic events in exosome-treated cultures, in agreement with our histochemical analysis (Fig. 5E , lower panel ).…”

Section: Resultssupporting

confidence: 85%

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

et al. 2022

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Seizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7–12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca2+ imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7–12 when the threshold for spike initiation is significantly reduced. At DIV 7–12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.

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Section: Resultssupporting

confidence: 85%

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

et al. 2022

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“…Immunofluorescence staining was performed as described previously . Hippocampal cells were fixed in PBS containing 4% PFA for 20 min at RT.…”

Section: Methodsmentioning

confidence: 99%

“…The puff pipette, located at a distance of 200 μm from the recorded cell, was filled with extracellular solution (control), GO (200 μg/mL), GO–NPY (200 μg/mL and 10 μM, respectively), or NPY (10 μM), all diluted in extracellular saline solution. Considering the volume (1 mL) of the extracellular solutions in the recording chamber, the final concentration of conjugates (or control solutions) reaching the patch-clamped neurons was 10% of that present in the puff pipette . PSCs were recorded before and after (10 min each) the local ejection.…”

Section: Methodsmentioning

confidence: 99%

Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System

Cellot

Jacquemin

Reina

et al. 2022

ACS Appl. Nano Mater.

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Nanoscale graphene-based materials (GBMs) enable targeting subcellular structures of the nervous system, a feature crucial for the successful engineering of alternative nanocarriers to deliver drugs and to treat neurodisorders. Among GBMs, graphene oxide (GO) nanoflakes, showing good dispersibility in water solution and being rich of functionalizable oxygen groups, are ideal core structures for carrying biological active molecules to the brain, such as the neuropeptide Y (NPY). In addition, when unconjugated, these nanomaterials have been reported to modulate neuronal function per se. Although some GBM-based nanocarriers have been tested both in vitro and in vivo, a thorough characterization of covalent binding impact on the biological properties of the carried molecule and/or of the nanomaterial is still missing. Here, a copper(I)-catalyzed alkyne− azide cycloaddition strategy was employed to synthesize the GO−NPY complex. By investigating through electrophysiology the impact of these conjugates on the activity of hippocampal neurons, we show that the covalent modification of the nanomaterial, while making GO an inert platform for the vectorized delivery, enhances the duration of NPY pharmacological activity. These findings support the future use of GO for the development of smart platforms for nervous system drug delivery.

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“…In addition, through both in vitro and in vivo models, the role of GO-nanosheets/glutamate interference in the amygdala synaptic circuitry has been explored. An excessive glutamatergic activity in the lateral nucleus of the amygdala complex is involved in anxiety and post-traumatic stress disorder [ 58 , 59 ].…”

Section: Application Fieldsmentioning

confidence: 99%

“… Materials Characteristics Applications Ref. Chitosan Induce axonal growth Reduces tissue scarification Nerve grafts conduits [ 76 , 77 ] CNT Mechanical strength Thermal inertness Transparent nerve conduits Axon regeneration Spinal cord regeneration Implantable devices with suitable neural interfaces [ 62 , 63 , 64 ] Fibroin Elastic Flexible Highly resistant to stretching/compression Nerve grafts conduits Recovery of the median nerve [ 78 , 79 , 80 , 81 ] OG Mechanical strength Electrical and thermal conductivity Education of neural connections Guide neural growth and differentiation [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ] PBCA Biocompatible Neural differentiation Cell culture [ 98 ] …”

Section: Application Fieldsmentioning

confidence: 99%

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

Camponogara

Zanotti

Tiengo

et al. 2022

IJMS

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Regenerative medicine is the branch of medicine that effectively uses stem cell therapy and tissue engineering strategies to guide the healing or replacement of damaged tissues or organs. A crucial element is undoubtedly the biomaterial that guides biological events to restore tissue continuity. The polymers, natural or synthetic, find wide application thanks to their great adaptability. In fact, they can be used as principal components, coatings or vehicles to functionalize several biomaterials. There are many leading centers for the research and development of biomaterials in Italy. The aim of this review is to provide an overview of the current state of the art on polymer research for regenerative medicine purposes. The last five years of scientific production of the main Italian research centers has been screened to analyze the current advancement in tissue engineering in order to highlight inputs for the development of novel biomaterials and strategies.

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Thin graphene oxide nanoflakes modulate glutamatergic synapses in the amygdala cultured circuits: Exploiting synaptic approaches to anxiety disorders

Cited by 11 publications

References 37 publications

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System

Biomaterials for Regenerative Medicine in Italy: Brief State of the Art of the Principal Research Centers

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