Expression of Bruton´s tyrosine kinase in different type of brain lesions of multiple sclerosis patients and during experimental demyelination

BackgroundInhibition of Bruton’s tyrosine kinase (BTK) is an emerging multiple sclerosis (MS) therapy. BTK inhibitors (BTKi) cross the blood-brain barrier and modulate B cells and microglia, major cellular players in active and chronic active lesions.ObjectiveTo assess potential lesional and cellular targets of BTKi, we examined BTK expression in different type of MS white matter (WM) lesions, in unmanipulated CNS resident cells, and in a degenerative MS model associated with microglia activation in vivo.MethodsWe examined BTK expression by next-generation RNA-sequencing in postmortem 25 control WM, 19 NAWM, 6 remyelinating, 18 active, 13 inactive and 17 chronic active lesions. Presence of B cells and microglia were examined by immunohistochemistry. CNS resident cells were isolated from the mouse brain by magnetic sorting. BTK expression was examined by quantitative PCR in isolated cells and dissected corpus callosum from mice treated with cuprizone (CPZ).ResultsBTK expression was significantly increased in active and chronic active lesions with upregulated complement receptors and Fcγ receptors. Active lesions contained high number of perivascular B cells, microglia, and macrophages. Chronic active lesions were characterized by microglia/macrophages in the rim. Microglia expressed BTK at high level (120-fold) in contrast to other CNS cell types (2-4-fold). BTK expression was increasing during CPZ treatment reaching significance after stopping CPZ.ConclusionConsidering BTK expression in MS lesions and resident cells, BTKi may exert effect on B cells, microglia/macrophages in active lesions, and limit microglia activation in chronic active lesions, where tissue damage propagates

ManyBabies 5: A large-scale investigation of the proposed shift from familiarity preference to novelty preference in infant looking time Pre-data collection manuscript for peer-review The ManyBabies 5 Team

International audienceMuch of our basic understanding of cognitive and social processes in infancy relies on measures of looking time, and specifically on infants' visual preference for a novel or familiar stimulus. However, despite being the foundation of many behavioral tasks in infant research, the determinants of infants' visual preferences are poorly understood, and differences in the expression of preferences can be difficult to interpret. In this large-scale study, we test predictions from the Hunter and Ames model of infants' visual preferences. 1 We investigate the effects of three factors predicted by this model to determine infants' preference for novel versus familiar stimuli: age, stimulus familiarity, and stimulus complexity. Drawing from a large and diverse sample of infant participants (N = XX), this study will provide crucial empirical evidence for a robust and generalizable model of infant visual preferences, leading to a more solid theoretical foundation for understanding the mechanisms that underlie infants' responses in common behavioral paradigms. Moreover, our findings will guide future studies that rely on infants' visual preferences to measure cognitive and social processes

ManyBabies 5: A large-scale investigation of the proposed shift from familiarity preference to novelty preference in infant looking time

Much of our basic understanding of cognitive and social processes in infancy relies on measures of looking time, and specifically on infants’ visual preference for a novel or familiar stimulus. However, despite being the foundation of many behavioral tasks in infant research, the determinants of infants’ visual preferences are poorly understood, and differences in the expression of preferences can be difficult to interpret. In this large-scale study, we test predictions from the Hunter and Ames model of infants' visual preferences. We investigate the effects of three factors predicted by this model to determine infants’ preference for novel versus familiar stimuli: age, stimulus familiarity, and stimulus complexity. Drawing from a large and diverse sample of infant participants (minimum expected sample size N = 1,280), this study aims to provide empirical evidence for a robust and generalizable model of infant visual preferences, leading to a more solid theoretical foundation for understanding the mechanisms that underlie infants’ responses in common behavioral paradigms. Moreover, we hope that our findings will guide future studies that rely on infants' visual preferences to measure cognitive and social processes