BDNF and TrkB in neuronal differentiation of Fmr1-knockout mouse.

摘要: Fragile X syndrome (FXS) is a common cause of inherited mental retardation and the best characterized form autistic spectrum disorders. FXS caused by loss functional fragile protein (FMRP), which leads to abnormalities in differentiation neural progenitor cells (NPCs) development dendritic spines neuronal circuits. Brain-derived neurotrophic factor (BDNF) its TrkB receptors play central role maturation plasticity. We studied BDNF/TrkB actions absence FMRP show that an increase catalytic expression undifferentiated NPCs Fmr1-knockout (KO) mice, mouse model for FXS, associated with changes migration neurons expressing neurosphere cultures developing cortex. Aberrant intracellular calcium responses BDNF ATP subpopulations differentiating combined suggest cell subtype-specific alterations during early FMRP. Furthermore, we targeting Bdnf mRNA was increased under basal conditions further enhanced cortical layer V hippocampal CA1 Fmr1-KO mice pilocarpine-induced activity represented convulsive seizures, suggesting BDNF/TrkB-mediated feedback mechanisms strengthening synapses were compromised Pilocarpine-induced seizures accumulation transcripts most proximal segments dendrites but not mice. In addition, levels hippocampus reduced cortex line regional differences synaptic plasticity brain Altogether, present data signaling modulate impair FXS.