Intranasal Inhibition of Tropomyosin Receptor Kinase B Signaling during Early Postnatal Development Disrupts Growth and Sensorimotor Maturation in Neonatal Rodents.

introductionBrain-derived neurotrophic factor and its receptor, tropomyosin receptor kinase B (TrkB), are critical regulators of neuronal growth, synaptic plasticity, and behavioral maturation during early development. The present study investigated how postnatal inhibition of TrkB signaling influences early neurobehavioral outcomes in neonatal rodents.

methodsNeonatal pups received daily intranasal administration of either saline or the TrkB antagonist ANA-12 (0.5 mg/kg or 1 mg/kg) on postnatal days 8-14 and were assessed for body weight gain, reflex development, and neuroinflammatory markers in cortical and hippocampal tissue.

resultsANA-12 treatment reduced body weight gain and delayed performance in righting, negative geotaxis, and cliff avoidance tasks. Total TrkB expression was significantly increased following ANA-12 treatment, while phosphorylated TrkB levels were unchanged; however, the ratio of phosphorylated to total TrkB was reduced. Inflammatory responses were region- and cytokine-specific, with significant reductions in hippocampal IL-6 and TNF-α, and a selective reduction in cortical TNF-α at the higher dose, while cortical IL-6 was not significantly altered.

conclusionThese findings indicate that TrkB inhibition during early development disrupts neurobehavioral maturation, alters receptor expression and activation balance, and modulates inflammatory signaling in a region-specific manner.