Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro

Multiple sclerosis is characterized by tissue atrophy involving the brain and the spinal cord, where reactive inflammation contributes to the neurodegenerative processes. Recently, the presence of synapse alterations induced by the inflammatory responses was suggested by experimental and clinical observations, in experimental autoimmune encephalomyelitis mouse model and in patients, respectively. Further knowledge on the interplay between pro-inflammatory agents, neuroglia and synaptic dysfunction is crucial to the design of unconventional protective molecules. Here we report the effects, on spinal cord circuits, of a cytokine cocktail that partly mimics the signature of T lymphocytes sub population Th1. In embryonic mouse spinal organ-cultures, containing neuronal cells and neuroglia, cytokines induced inflammatory responses accompanied by a significant increase in spontaneous synaptic activity. We suggest that cytokines specifically altered signal integration in spinal networks by speeding the decay of GABAA responses. This hypothesis is supported by the finding that synapse protection by a non-peptidic NGF mimetic molecule prevented both the changes in the time course of GABA events and in network activity that were left unchanged by the cytokine production from astrocytes and microglia present in the cultured tissue. In conclusion, we developed an important tool for the study of synaptic alterations induced by inflammation, that takes into account the role of neuronal and not neuronal resident cells

Hybrid Interfaces Made of Nanotubes and Backbone-Altered Dipeptides Tune Neuronal Network Architecture

Peptides constituted of backbone homologated α-amino acids combined with carbon materials offer interesting possibilities in the modulation of cellular functions. In this work, we have prepared diphenylalanine β- and γ-peptides and conjugated them to carbon nanotubes (CNTs). These hybrids were able to self-assemble into fibrillar dendritic structures enabling the growth of primary hippocampal cells and the modulation of their neuronal functions. In particular, following the deposition of the different nanomaterials on glass substrates, we have evaluated their effects on circuit function and geometry. The geometrical restrictions due to CNT nucleated nodes allowed growth of neuronal networks with control over network geometry, and exploring its functional impact. In diverse applications from basic neuroscience, the presence of CNT nodes may be exploited in brain interfaces able to convey highly localized electrical stimuli

Functional rewiring across spinal injuries via biomimetic nanofiber scaffolds

The regrowth of severed axons is fundamental to reestablish motor control after spinal-cord injury (SCI). Ongoing efforts to promote axonal regeneration after SCI have involved multiple strategies that have been only partially successful. Our study introduces an artificial carbon-nanotube based scaffold that, once implanted in SCI rats, improves motor function recovery. Confocal microscopy analysis plus fiber tracking by magnetic resonance imaging and neurotracer labeling of long-distance corticospinal axons suggest that recovery might be partly attributable to successful crossing of the lesion site by regenerating fibers. Since manipulating SCI microenvironment properties, such as mechanical and electrical ones, may promote biological responses, we propose this artificial scaffold as a prototype to exploit the physics governing spinal regenerative plasticity

Hybrid Interfaces Made of Nanotubes and Backbone-Altered Dipeptides Tune Neuronal Network Architecture

Peptides constituted of backbone homologated \u3b1-amino acids combined with carbon materials offer interesting possibilities in the modulation of cellular functions. In this work, we have prepared diphenylalanine \u3b2- and \u3b3-peptides and conjugated them to carbon nanotubes (CNTs). These hybrids were able to self-assemble into fibrillar dendritic structures enabling the growth of primary hippocampal cells and the modulation of their neuronal functions. In particular, following the deposition of the different nanomaterials on glass substrates, we have evaluated their effects on circuit function and geometry. The geometrical restrictions due to CNT nucleated nodes allowed growth of neuronal networks with control over network geometry, and exploring its functional impact. In diverse applications from basic neuroscience, the presence of CNT nodes may be exploited in brain interfaces able to convey highly localized electrical stimuli

Additional file 2: of Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro

The frequency and amplitude of GABAergic PSCs were not affected by CKs treatments in the absence of in the presence of MT2. Box-plots summarize the frequency (A) and the amplitude (B) of IPSCs prior and after CKs incubation in both the absence and the presence of MT2. (C) The plots show the absence of linear correlation between the decay time constant and rise time of IPSCs in all the conditions tested. (TIFF 777 kb

Additional file 2: of Bridging pro-inflammatory signals, synaptic transmission and protection in spinal explants in vitro

The frequency and amplitude of GABAergic PSCs were not affected by CKs treatments in the absence of in the presence of MT2. Box-plots summarize the frequency (A) and the amplitude (B) of IPSCs prior and after CKs incubation in both the absence and the presence of MT2. (C) The plots show the absence of linear correlation between the decay time constant and rise time of IPSCs in all the conditions tested. (TIFF 777 kb