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Volume 17, Number 10, Issue of May 15, 1997 pp. 3623-3633
Copyright ©1997 Society for Neuroscience

TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death

Received Oct. 29, 1996; revised Feb. 18, 1997; accepted Feb. 24, 1997.

Soledad Alcántara1, Jonas Frisén2, José Antonio del Río1, Eduardo Soriano1, Mariano Barbacid2, and Inmaculada Silos-Santiago2

1 Department of Cell Biology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain, and 2 Department of Molecular Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000

Newborn mice carrying targeted mutations in genes encoding neurotrophins or their signaling Trk receptors display severe neuronal deficits in the peripheral nervous system but not in the CNS. In this study, we show that trkB (-/-) mice have a significant increase in apoptotic cell death in different regions of the brain during early postnatal life. The most affected region in the brain is the dentate gyrus of the hippocampus, although elevated levels of pyknotic nuclei were also detected in cortical layers II and III and V and VI, the striatum, and the thalamus. 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 through TrkB receptors plays a role in the survival of CNS neurons during postnatal development. Moreover, they indicate that TrkB receptor signaling protects subpopulations of CNS neurons from injury- and axotomy-induced cell death.

Key words: TrkB; CNS; cell death; axotomy; hippocampus; motor neuron




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