Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats

Biagioni, Audrey Franceschi; Cellot, Giada; Pati, Elisa; Lozano, Neus; Ballesteros, Belén; Casani, Raffaele; Coimbra, Norberto Cysne; Kostarelos, Kostas; Ballerini, Laura

doi:10.1016/j.biomaterials.2021.120749

Cited by 16 publications

(49 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on our previous results ,− , describing the impact of graphene materials on neuronal functions, we have selected a nanoscale GO obtained by Hummers’ oxidation of graphite for combination with the NPY peptide. The single layer of GO sheets possessed a size distribution centered at 430 nm .…”

Section: Resultsmentioning

confidence: 99%

“…Next, we studied the effects of the conjugate on synaptic currents through the patch clamp technique. Because pristine GO flakes were reported to modify neuronal activity per se − the first set of experiments was aimed to understand if GO sheets, when conjugated to a peptide, retained their modulatory action on neurons. We exposed voltage-clamped neurons to short (500 ms) pressure ejections (puffs) of GO, GO–NPY, NPY, or saline solution, used as control, positioning a second pipette close to the recorded neuron (sketched in Figure b; see the Experimental Section , ).…”

Section: Resultsmentioning

confidence: 99%

“…Because GO has been recently reported to tune neuronal activity, − the aim of our study was to investigate whether when this nanomaterial is engineered in a drug delivery context it could contribute to the biological activity of the conjugates. The starting point was to determine the type of linkage between the GO and NPY peptide.…”

Section: Discussionmentioning

confidence: 99%

“…Among GBMs, GO has received extensive attention in this field due to its good dispersibility in aqueous media, − a feature crucial for drug delivery applications, and to its wealth of oxygen containing functional groups making it easy to bind biomolecules such as genes, drugs, antibodies, or peptides . In addition, pristine GO nanoflakes have been reported to target precisely synapses tuning neuronal activity in vitro and in vivo − making this nanomaterial interesting not only for the delivery of drugs but also as the active ingredient per se .…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Graphene is an atomically-thin carbon-based nanomaterial currently exploited in many research fields ( Randviir et al, 2014 ), as well as industrial sectors ( Zhou et al, 2011 ; Torrisi et al, 2012 ), including advanced biomedical applications ( Ryoo et al, 2010 ; Nayak et al, 2011 ; Zhang et al, 2011 ; Reina et al, 2017 ). In regard to the latter application, graphene unusual physicochemical properties, such as its high carrier mobility, optical transparency and ease of chemical functionalization, open to novel approaches in the design and fabrication of advanced neuronal tools as, for example, implanted brain sensors, smart stimulation electrodes or neuroprosthetic devices ( Lu et al, 2016 ; Shin et al, 2016 ; Franceschi Biagioni et al, 2021 ). In this framework, the possibility to layer graphene on virtually every surface and its ease of chemical functionalization ( Xu et al, 2016 ), drastically expands material capabilities making it possible, for example, to design devices able to tune cellular adhesion ( Jeong et al, 2016 ), reduce inflammatory responses ( Zhou et al, 2016 ), or introduce chemical moieties ( Karki et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Bidirectional Modulation of Neuronal Cells Electrical and Mechanical Properties Through Pristine and Functionalized Graphene Substrates

et al. 2022

View full text Add to dashboard Cite

In recent years, the quest for surface modifications to promote neuronal cell interfacing and modulation has risen. This course is justified by the requirements of emerging technological and medical approaches attempting to effectively interact with central nervous system cells, as in the case of brain-machine interfaces or neuroprosthetic. In that regard, the remarkable cytocompatibility and ease of chemical functionalization characterizing surface-immobilized graphene-based nanomaterials (GBNs) make them increasingly appealing for these purposes. Here, we compared the (morpho)mechanical and functional adaptation of rat primary hippocampal neurons when interfaced with surfaces covered with pristine single-layer graphene (pSLG) and phenylacetic acid-functionalized single-layer graphene (fSLG). Our results confirmed the intrinsic ability of glass-supported single-layer graphene to boost neuronal activity highlighting, conversely, the downturn inducible by the surface insertion of phenylacetic acid moieties. fSLG-interfaced neurons showed a significant reduction in spontaneous postsynaptic currents (PSCs), coupled to reduced cell stiffness and altered focal adhesion organization compared to control samples. Overall, we have here demonstrated that graphene substrates, both pristine and functionalized, could be alternatively used to intrinsically promote or depress neuronal activity in primary hippocampal cultures.

show abstract

Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model

Tortella,

Santini,

Lozano

et al. 2023

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

Small graphene oxide (s‐GO) nanosheets reversibly downregulate central nervous system (CNS) excitatory synapses, with potential developments as future therapeutic tools to treat neuro‐disorders characterized by altered glutamatergic transmission. Excitotoxicity, namely cell death triggered by exceeding ambient glutamate fueling over‐activation of excitatory synapses, is a pathogenic mechanism shared by several neural diseases, from ischemic stroke to neurodegenerative disorders. Here we exposed CNS cultures to oxygen‐glucose deprivation (OGD) to mimic ischemic stroke in vitro, and we show that the delivery of s‐GO following OGD, during the endogenous build‐up of secondary damage and excitotoxicity, improved neuronal survival. In a different paradigm, we reproduced excitotoxicity cell damage through exogenous glutamate application, and we observed that s‐GO co‐treatment protected neuronal integrity, potentially by directly downregulating the synaptic over‐activation brought about by exogenous glutamate. In our proof‐of‐concept study we suggest that s‐GO may find novel applications in therapeutic developments for treating excitotoxicity‐driven neural cell death.

show abstract

Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats

Cited by 16 publications

References 52 publications

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

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

Bidirectional Modulation of Neuronal Cells Electrical and Mechanical Properties Through Pristine and Functionalized Graphene Substrates

Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model

Contact Info

Product

Resources

About