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Free keywords:
AMYOTROPHIC-LATERAL-SCLEROSIS; CULTURED CORTICAL-NEURONS; NEUROTROPHIC
FACTOR; MELANOCORTIN-4 RECEPTOR; SPINAL MOTONEURONS; DENDRITIC GROWTH;
TRANSGENIC MICE; ENERGY-BALANCE; NADPH OXIDASE; BRAINBiochemistry & Molecular Biology; Genetics & Heredity;
Abstract:
Brain-derived neurotrophic factor (BDNF) and its receptor
tropomyosin-related kinase B (TrkB) are widely expressed in the
vertebrate nervous system and play a central role in mature neuronal
function. In vitro BDNF/TrkB signaling promotes neuronal survival and
can help neurons resist toxic insults. Paradoxically, BDNF/TrkB
signaling has also been shown, under certain in vitro circumstances, to
render neurons vulnerable to insults. We show here that in vivo
conditional deletion of TrkB from mature motor neurons attenuates
mutant superoxide dismutase 1 (SOD1) toxicity. Mutant SOD1 mice lacking
motor neuron TrkB live a month longer than controls and retain motor
function for a longer period, particularly in the early phase of the
disease. These effects are subserved by slowed motor neuron loss,
persistence of neuromuscular junction integrity and reduced astrocytic
and microglial reactivity within the spinal cord. These results suggest
that manipulation of BDNF/TrkB signaling might have therapeutic
efficacy in motor neuron diseases.
