The expression of brain-derived neurotrophic factor (BDNF) mRNA and the secretion of BDNF protein are tightly regulated by neuronal activity. Thus, BDNF has been proposed as a mediator of activity-dependent neural plasticity. Previous studies showed that dark rearing (DR) reduces BDNF mRNA levels in the primary visual cortex (V1), but the effects of visual experience on BDNF protein levels are unknown. We report that rearing in constant light or DR alters BDNF mRNA and protein levels in the retina, superior colliculus (SC), V1, hippocampus (HIPP), and cerebellum (CBL), although the changes in mRNA and protein are not always correlated. Most notably, DR increases BDNF protein levels in V1 although BDNF mRNA is decreased. BDNF protein levels also undergo diurnal changes. In the retina, V1, and SC, BDNF protein levels are higher during the light phase of the circadian cycle than during the dark phase. By contrast, in HIPP and CBL, the tissue concentration of BDNF protein is higher during the dark phase. The discrepancies between the experience-dependent changes in BDNF mRNA and protein suggest that via its effects on neuronal activity, early sensory experience alters the trafficking, as well as the synthesis, of BDNF protein. The circadian changes in BDNF protein suggest that BDNF could cause the diurnal modulation of synaptic efficacy in some neural circuits. The fluctuations in BDNF levels in nonvisual structures suggest a potential role of BDNF in mediating plasticity induced by hormones or motor activity.
Developing neurons depend on many target-derived signals. One of these signals is the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous application of BDNF in vitro and in vivo rescues a population of lumbar motoneurons from programmed cell death. Given that BDNF does not rescue all motoneurons and that motoneurons differ in trophic factor receptor expression, subpopulations of motoneurons may have different sensitivities to the factor. These differences may be reflected in distinct target muscles specialized to produce different protein concentrations, or muscles may contain equal amounts of the factor and receptor expression determines motoneuron responsiveness. By using a sensitive electrochemiluminescent immunoassay (ECLIA), we measured normal developmental changes in BDNF protein concentration in anatomically and functionally distinct chick embryonic thigh muscles from E6 to E18. We found that there were no significant differences in BDNF protein concentration between muscles classified according to function (fast vs. slow) or anatomical position (flexor vs. extensor) and that the quantity of BDNF in the target did not appear to be activity dependent. These results suggest that, during development, the differences in the response of motoneurons to BDNF are not due to the anatomical or functional diversity of muscle targets. J. Comp. Neurol. 470:330-337, 2004.
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