Differential expression of brain-derived neurotrophic factor, neurotrophin-3, and low-affinity nerve growth factor receptor during the postnatal development of the rat cerebellar system

Abstract

The spatio-temporal pattern of expression of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF) and low-affinity nerve growth factor receptor (LNGFR) genes was analyzed in the postnatal developing cerebellar system of the rat by in situ hybridization histochemistry. Different ontogenetic patterns of expression were observed for these three genes. In agreement with previously published results ( Neuron, 5 (1990) 501–509; Dev. Brain Res., 55 (1990) 288–292) we found that NT3 and LNGFR mRNA peaked early, during the first 2 postnatal weeks, whereas BDNF mRNA peaked later, around postnatal day 20, in the cerebellar cortex. High levels of NT3 mRNA were found in the internal granule cell layer as early as postnatal day 5. NT3 mRNA was also present in the external-premigratory granule cell layer at postnatal day 10. From postnatal day 5 on, LNGFR mRNA was present in the proliferative area of the external granule cell layer and in the Purkinje cells. NT3 mRNA level decreased and BDNF mRNA increased in granule cells concomitantly with their migration and maturation, suggesting a sequential stimulation of these two genes during this developmental process. LNGFR mRNA levels decreased along the same period. Although practically undetectable in the cerebellar granule cell layer in the first two postnatal weeks, BDNF mRNA was transiently expressed in the deep cerebellar nuclei during this time and it was very abundant in the inferior olivary system from postnatal day 5 on. LNGFR mRNA was transiently expressed in the inferior olivary system, in the first postnatal week. These data are discussed in relation to the coordinated postnatal maturation of the different cells of the cerebellar system. Our results are compatible with a local delivery and role of NT3 in the early postnatal development of the cerebellar cortex. Its presence may be involved in the process of granule cell migration and/or the establishment of early synaptic contacts. BDNF, on the contrary, could play a role at a later stage, perhaps as a maintenance factor.