TRKB SIGNALING IS REQUIRED FOR POSTNATAL SURVIVAL OF CNS NEURONS AND PROTECTS HIPPOCAMPAL AND MOTOR-NEURONS FROM AXOTOMY-INDUCED CELL-DEATH

Newborn mice carrying targeted mutations in genes encoding neurotrophi ns or their signaling Trk receptors display severe neuronal deficits i n the peripheral nervous system but not in the CNS. In this study, we show that trkB (-/-) mice have a significant increase in apoptotic cel l death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hip pocampus, although elevated levels of pyknotic nuclei were also detect ed in cortical layers II and III and V and VI, the striatum, and the t halamus. Furthermore, axotomized hippocampal and motor neurons of trkB (-/-) mice have significantly lower survival rates than those of wild -type littermates. These results suggest that neurotrophin signaling t hrough TrkB receptors plays a role in the survival of CNS neurons duri ng postnatal development. Moreover, they indicate that TrkB receptor s ignaling protects subpopulations of CNS neurons from injury- and axoto my-induced cell death.