Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons.

AIMS: The crucial step in the pathogenic events that lead to the development and the progression of multiple sclerosis (MS) is the infiltration of autoreactive T cells in the brain. Data from experimental autoimmune encephalomyelitis (EAE) mice indicate that, together with microglia, T cells are responsible for the enhancement of the glutamatergic transmission in central neurons, contributing to glutamate-mediated excitotoxicity, a pathological hallmark of both EAE and MS brains. Here, we addressed the synaptic role of T cells taken from MS patients. METHODS: A chimeric model of human T cells and murine brain slices was established to record, by Patch Clamp technique, the glutamatergic transmission in the presence of T cells isolated from the peripheral blood of healthy subjects (HS), active (a) and nonactive (na) relapsing remitting MS patients. Intracellular staining and flow cytometry were used to assess tumour necrosis factor (TNF) expression in T cells. RESULTS: Chimeric experiments indicated that, compared to HS and naMS, T cells from aMS induced an increase in glutamatergic kinetic properties of striatal neurons. Such alteration, reminiscent of the those induced by EAE T cells, was blocked by incubation of the slices with etanercept, a TNF receptor antagonist. Of note, T cells from aMS expressed more TNF than naMS patients and HS subjects. CONCLUSION: These data highlight the synaptotoxic potential retained by MS T cells, suggesting that during the inflammatory phase of the disease infiltrating T cells could influence the neuronal activity contributing to the TNF-mediated mechanisms of glutamate excitotoxicity in central neurons.

Familiarity for famous faces and names is not equally subtended by the right and left temporal poles. Evidence from an rTMS study.

The aims of the present experiment was to investigate: (a) if transient disruption of neural activity in the right (RTP) or left temporal pole (LTP) can interfere with the development of a familiarity feeling to the presentation of faces/written names of famous/unknown people; and (b) if this interference specifically affects the familiarity for faces after inhibition of the RTP and for names after inhibition of the LTP. Twenty healthy volunteers took part in the study. Repetitive transcranial magnetic stimulation (rTMS) was administered online; it disrupted the neural activity of the right or left TP in concomitance with the presentation of each face and name whose familiarity had to be assessed. Furthermore, in a control group, each participant was submitted to a single experimental session in which rTMS was delivered to the vertex in association with the presentation of faces and written names. Since previous rTMS studies have shown that the temporary inactivation of the right and left TP influences the response latencies, but not the number of correct responses, in this study we took into account both the number of correct responses obtained in different experimental conditions and the corresponding response latencies. A three-way factorial ANOVA carried out on the Response Scores showed only a general effect of the Type of Stimuli, due to better performances on names than on faces. This greater familiarity of names is consistent with previous data reported in the literature. In the three-way factorial ANOVA carried out on the Latency Scores, post-hoc analyses showed an increased latency of responses to faces after right stimulation in Latency Total, Latency on Correct responses and Latency on Unfamiliar faces. None of these results were obtained in the control group. These data suggest that rTMS at the level of the RTP preferentially affects the development of familiarity feelings to the presentation of faces of famous people.