Study of Effector CD8+ T Cell Interactions with Cortical Neurons in Response to Inflammation in Mouse Brain Slices and Neuronal Cultures.

Cytotoxic CD8+ T cells contribute to neuronal damage in inflammatory and degenerative CNS disorders, such as multiple sclerosis (MS). The mechanism of cortical damage associated with CD8+ T cells is not well understood. We developed in vitro cell culture and ex vivo brain slice co-culture models of brain inflammation to study CD8+ T cell-neuron interactions. To induce inflammation, we applied T cell conditioned media, which contains a variety of cytokines, during CD8+ T cell polyclonal activation. Release of IFNγ and TNFα from co-cultures was verified by ELISA, confirming an inflammatory response. We also visualized the physical interactions between CD8+ T cells and cortical neurons using live-cell confocal imaging. The imaging revealed that T cells reduced their migration velocity and changed their migratory patterns under inflammatory conditions. CD8+ T cells increased their dwell time at neuronal soma and dendrites in response to added cytokines. These changes were seen in both the in vitro and ex vivo models. The results confirm that these in vitro and ex vivo models provide promising platforms for the study of the molecular details of neuron-immune cell interactions under inflammatory conditions, which allow high-resolution live microscopy and are readily amenable to experimental manipulation.

Inspiratory Muscle Training Improves Aerobic Fitness in Active Children.

Research on the effect of inspiratory muscle training (IMT) on exercise performance is inconsistent. IMT has not been applied to fit child athletes, who are more likely to develop inspiratory muscle fatigue, and, consequently, to benefit from IMT. Methods: Thirty children (mean age: 10.7 ± 1.2 years) were recruited and randomly assigned to a high-intensity (HG), a low-intensity (LG), or a control group (CG). For both training groups, a double-blind procedure was applied. In the HG, 80% of maximal inspiratory pressure (MIP) was used as the level of training intensity. The LG used 30% MIP. Training groups were trained at 6 breaths a set, 4 sets a day, totaling 24 breaths a day for 6 weeks. Exercise capacity outcomes include maximal and submaximal aerobic capacity, as measured as VO2max and distance from six-minute walk test (6MWD). Results show improvement in MIP, VO2max, and 6MWD only in the HG. MIP in the HG significantly increases from 108.7 (100.8-143.3) to 144.4 (130.0-175.6) cmH2O. VO2max in the HG increases from 43.0 (40.5-45) to 53.0 (46-63) mL·kg-1·min-1. The 6MWD increases from 792.0 (737.5-818.0) to 862.0 (798.5-953.5) m. Data are presented as median (interquartile range). No difference is found in the LG or CG. Conclusion: high-intensity IMT increases MIP, maximal, and submaximal exercise capacity in the HG, but no difference is found in the LG or CG. Therefore, high-intensity type of IMT improves aerobic fitness in fit children by appropriately applying inspiratory muscle strength training.

Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior.

Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.