Biology subjects

Spinelli, G.

Publications and source records attributed to Spinelli, G..

4 recordsLinked to original sources

bioRxiv2026

Triptans reprogram Schwann cells to drive medication-overuse headache via β-glycan/TGF-β3 signaling

Medication-overuse headache (MOH) is one of the leading causes of chronic daily headache worldwide and arises from the repeated use of acute anti-migraine medications, including triptans. However, the cellular substrates and intracellular pathways driving this paradoxical chronification remain unknown. Here, using Schwann cell-selective silencing of the 5-HT1B/D receptor, we observed that acute triptan administration counteracts CGRP-induced, endosome-confined cAMP accumulation, preventing the development of periorbital mechanical allodynia in mice. In contrast, prolonged 5-HT1B/D activation in Schwann cells induces epigenetic and transcriptomic dysregulation associated with MOH in mice. Specifically, intronic hypermethylation-driven overexpression of BETAGLYCAN promotes activation of a non-canonical TGF-{beta}-dependent signaling cascade. The resulting TGF-{beta}3 upregulation establishes a feed-forward loop that sustains proalgesic paracrine communication between Schwann cells and primary sensory neurons. Analysis of plasma levels from patients with MOH confirmed elevated TGF-{beta}3 levels specifically associated with triptan-dependent MOH, supporting the translational relevance of these findings. Together, our data identify Schwann cell 5-HT1B/D signaling as a dual mediator of both the acute anti-migraine efficacy and the maladaptive mechanisms underlying MOH. These results provide a conceptual framework for strategies aimed at preserving the therapeutic benefits of triptans while limiting the adverse consequences of chronic administration. One Sentence SummarySchwann cell 5-HT1B/D receptor signaling mediates the dual effects of triptans by acutely inhibiting CGRP-driven nociceptive pathways while chronically promoting epigenetically driven TGF-{beta}3-dependent proalgesic signaling that causes medication-overuse headache.

pharmacology and toxicology↗

bioRxiv2022

Theta band-power shapes amyloid-driven longitudinal EEG changes in pre-clinical Alzheimer's Disease

Alzheimers Disease (AD) includes progressive symptoms spread along a continuum of pre-clinical (pre-AD) and clinical stages. Pre-AD refers to cognitively healthy individuals with presence of positive pathophysiological biomarkers of AD (i.e., markers of amyloidopathy and tauopathy). Although numerous studies uncovered the neuro-cognitive changes of AD, very little is known on the natural history of brain lesions and modifications of brain networks of pre-AD. To address this issue, we analysed resting-state EEG data of 318 cognitively healthy individuals with subjective memory complains from the INSIGHT-preAD cohort at the time of their first visit (M0) and two-years later (M24). Using 18F-florbetapir PET-scanner, subjects were stratified between amyloid positive (A-; n=230) and amyloid negative (A+; n=88) groups. Differences between A+ and A- individuals were estimated at source level in each band of the EEG power spectrum. At M0, we found an increase of theta-band power in the mid-frontal cortex in A+ compared to A-. No significant association was found between mid-frontal theta power and the individuals cognitive performance. While the very same effect was not replicated at M24, theta-band power increased in A+ relative to A- individuals in the posterior cingulate cortex and the pre-cuneus. Furthermore, alpha band revealed a peculiar decremental trend in posterior brain regions in the A+ relative to the A- group only at M24. These results provide the first source-level longitudinal evidence on the impact of brain amyloidosis on the EEG dynamics of a large-scale, monocentric cohort of pre-AD. Theta-band power increase over the mid-frontal and mid-posterior cortices suggests an hypoactivation of the default-mode network in individuals at-risk of AD and a non-linear longitudinal progression of the AD-spectrum.

neuroscience↗

bioRxiv2020

Selective neuromodulation induced by alpha-based neurofeedback learning: A double-blind randomized study

The neuromodulation induced by neurofeedback training (NFT) remains a matter of debate. Investigating the modulation of brain activity specifically associated with NF requires controlling for multiple factors, such as reward, performance, congruency between task and targeted brain activity. This can be achieved using sham feedback (FB) control condition, equating all aspects of the experiment but the link between brain activity and FB. We aimed at investigating the modulation of individual alpha EEG activity induced by NFT in a double-blind, randomized, sham-controlled study. Forty-eight healthy participants were assigned to either NF (n=25) or control (n=23) group and performed alpha upregulation training (over 12 weeks) with a wearable EEG device. Participants of the NF group received FB based on their individual alpha activity. The control group received the auditory FB of participants of the NF group. An increase of alpha activity across training sessions was observed in the NF group only (p<0.001). This neuromodulation was selective in that it was not observed for theta (4-8Hz) and low beta (13-18Hz) activities. While alpha upregulation was found in the NF group only, psychological outcome variables showed increased feeling of control, decreased anxiety level and increased relaxation feeling in both the NF and control groups, without any significant difference between groups. This is interpreted in terms of learning context and placebo effects. Our results pave the way to self-learnt, NF-based neuromodulation with light-weighted, wearable EEG systems.

neuroscience↗

bioRxiv2020

Validation of melomind(TM) signal quality: a proof of concept resting-state and ERPs study

Wearable EEG systems have become accessible to researchers and clinicians over the last decade, thus requiring neurotechnology companies to seek for outstanding EEG signal quality. Here, we show that the melomind headset equipped with dry electrodes (myBrain Technologies, Paris, France) allows the recording of reliable electro-cortical dynamics as compared to a wet-based standard-EEG system (actiCAP, Brain Products GmbH, Gilching, Germany). EEGs were acquired simultaneously from the two systems while thirteen subjects underwent a visual oddball, a steady-state visually-evoked potentials (SSVEPs) and two resting-state (RS) tasks. RS were acquired with eyes-closed and eyes-open (2 minutes each) and repeated twice (before and after the cognitive tasks). During the oddball task, participants responded on a gamepad when a target-stimulus was displayed. In the SSVEPs, visual responses were elicited at 15 and 20 Hz through a series of 15-second stimuli presented 5 times each. The power of theta- [4-8 Hz], alpha- [8-13 Hz], and beta- [13-30 Hz] band was extracted from the two RS. The signal-to-noise-ratio in the 15 ({+/-} 1) and 20 ({+/-} 1) Hz range was computed from the SSVEPs. The shape of the N2/P300 complex was analysed from the oddball task. Strong correlations resulted between the parameters obtained from the two EEG systems (0.53 < Pearsons r < 0.97). Bland and Altman analysis revealed small dissimilarities between the two systems, with values laying in the 95% confidence interval in all the tasks. Our results demonstrate that the melomind is an affordable solution to reliably assess humans electro-cortical dynamics at-rest and during cognitive tasks, thus paving the way to its use in neuroscience studies and brain-computer interfaces.

neuroscience↗