MAST CELL ACTIVATION DURING NEURODEVELOPMENT HAS LONG-TERM IMPACTS ON GLIAL CELLS AND BEHAVIOR IN MICE

Mast cells are immune system cells that, once activated, act by releasing inflammatory mediators and neuroactive substances, thereby establishing a communication axis with glial cells and enabling them to modulate physiological processes in the central nervous system (CNS). Although the presence of mast cells in the CNS during early developmental periods is well established, their role in neurodevelopment remains uncertain. Therefore, the present study aims to investigate how mast cell activation during neurodevelopment may modulate cellularity and long-term behavior in murine models. To this end, Swiss mice (CEUA #036/24) received intracerebroventricular injections of either 2 µg of compound C48/80, which promotes mast cell degranulation, or 2 µL of sterile saline on the first postnatal day. We observed that mice exposed to the compound exhibited a 29.41% increase in the number of microglia in hippocampal regions (p < 0.005, n = 4, Student’s t-test) compared to controls, 13 days after injection.When the animals reached adulthood, only male mice exposed to C48/80 displayed impairments in social interaction tasks (n = 12 animals per group, two-way ANOVA, factors: group and condition; interaction: p = 0.002) and in adaptation during reversal learning in the Morris Water Maze (n = 12 animals per group, two-way ANOVA, factors: group and quadrant; interaction: p = 0.0013).In addition, three-dimensional reconstruction of pyramidal neurons from the somatosensory cortex was performed using Golgi-Cox staining. We observed an aberrant arborization profile in mice exposed to C48/80, in which neurons exhibited dendritic processes that were 33.8% longer and 39.3% more arborized compared to the control group (p < 0.05, n = 6, Student’s t-test).The observed effects suggest that mast cell activation during neurodevelopment may exert long-lasting effects on glial cells.