Incidence and severity of G6PI-induced arthritis are not increased in genetically distinct mouse strains upon aging.

BACKGROUND: The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains. METHODS: Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function. RESULTS: While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo. CONCLUSION: While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.

1 mA cathodal tDCS shows excitatory effects in children and adolescents: Insights from TMS evoked N100 potential.

In children and adolescents, 1 mA transcranial direct current stimulation (tDCS) may cause "paradoxical" effects compared with adults: both 1 mA anodal and cathodal tDCS increase amplitude of the motor evoked potential (MEP) as revealed by a single pulse transcranial magnetic stimulation (TMS) of the motor cortex. Here, EEG based evoked potentials induced by a single pulse TMS, particularly the N100 component as marker of motor cortex inhibition, were investigated in order to explain effects of tDCS on the developing brain. In nineteen children and adolescents (11-16 years old), 1 mA anodal, cathodal, or sham tDCS was applied over the left primary motor cortex for 10 min. The TMS-evoked N100 was measured by 64-channel EEG before and immediately after stimulation as well as every 10 min after tDCS for one hour. 1 mA Cathodal stimulation suppressed the N100 amplitude compared with sham stimulation. In contrast, anodal tDCS did not modify the N100 amplitude. It seems likely that the increase of the motor cortex activity under cathodal tDCS in children and adolescents as shown in previous studies can be attributed to a reduce inhibition. Based on TMS evoked N100, the study provides an insight into neuromodulatory effects of tDCS on the developing brain.

Ten minutes of 1 mA transcranial direct current stimulation was well tolerated by children and adolescents: Self-reports and resting state EEG analysis.

Transcranial direct current stimulation (tDCS) is a promising and well-tolerated method of non-invasive brain stimulation, by which cortical excitability can be modulated. However, the effects of tDCS on the developing brain are still unknown, and knowledge about its tolerability in children and adolescents is still lacking. Safety and tolerability of tDCS was assessed in children and adolescents by self-reports and spectral characteristics of electroencephalogram (EEG) recordings. Nineteen typically developing children and adolescents aged 11-16 years participated in the study. Anodal and cathodal tDCS as well as sham stimulation were applied for a duration of 10 min over the left primary motor cortex (M1), each with an intensity of 1 mA. Subjects were unable to identify whether they had received active or sham stimulation, and all participants tolerated the stimulation well with a low rate of adverse events in both groups and no serious adverse events. No pathological oscillations, in particular, no markers of epileptiform activity after 1mA tDCS were detected in any of the EEG analyses. In summary, our study demonstrates that tDCS with 1mA intensity over 10 min is well tolerated, and thus may be used as an experimental and treatment method in the pediatric population.

Stimulation intensities of transcranial direct current stimulation have to be adjusted in children and adolescents.

OBJECTIVE: The aim of the present study was to investigate the effect of the transcranial direct current stimulation (tDCS) on motor cortex excitability in healthy children and adolescents. METHODS: We applied 1mA anodal or cathodal tDCS for 10min on the left primary motor cortex of 19 healthy children and adolescents (mean age 13.9±0.4years). In order to prove whether the effects of tDCS may be attributed to the stimulation intensity, 10 children and adolescents were studied again using 0.5mA anodal and cathodal tDCS. Sham stimulation was used as a control. RESULTS: Compared with sham stimulation, both 1mA anodal and cathodal tDCS resulted in a significant increase of Motor evoked potentials (MEP) amplitudes which remained to be prominent even one hour after the end of stimulation. Interestingly, the 0.5mA cathodal tDCS decreased cortico-spinal excitability whereas the 0.5mA anodal stimulation did not result in any effect. CONCLUSION: For the first time, the study demonstrates age-specific influences of tDCS on cortical excitability of the primary motor cortex. SIGNIFICANCE: Thus, the stimulation protocols of the tDCS have to be optimized according to age by planning studies in pediatric population.