In Vivo Induction of Glial Cell Proliferation and Axonal Outgrowth and Myelination by Brain-Derived Neurotrophic Factor

Abstract

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of neuronal cell survival and differentiation factors but is thought to be involved in neuronal cell proliferation and myelination as well. To explore the role of BDNF in vivo, we employed the intermediate pituitary melanotrope cells of the amphibian Xenopus laevis as a model system. These cells mediate background adaptation of the animal by producing high levels of the prohormone proopiomelanocortin (POMC) when the animal is black adapted. We used stable X. transgenesis in combination with the POMC gene promoter to generate transgenic frogs overexpressing BDNF specifically and physiologically inducible in the melanotrope cells. Intriguingly, an approximately 25-fold overexpression of BDNF resulted in hyperplastic glial cells and myelinated axons infiltrating the pituitary, whereby the transgenic melanotrope cells became located dispersed among the induced tissue. The infiltrating glial cells and axons originated from both peripheral and central nervous system sources. The formation of the phenotype started around tadpole stage 50 and was induced by placing white-adapted transgenics on a black background, i.e. after activation of transgene expression. The severity of the phenotype depended on the level of transgene expression, because the intermediate pituitaries from transgenic animals raised on a white background or from transgenics with only an approximately 5-fold BDNF overexpression were essentially not affected. In conclusion, we show in a physiological context that, besides its classical role as neuronal cell survival and differentiation factor, in vivo BDNF can also induce glial cell proliferation as well as axonal outgrowth and myelination.

Astrocytes, but not olfactory ensheathing cells or Schwann cells, promote myelination of CNS axons in vitro

“…OPC numbers then dropped to a significantly lower number than that seen on NsAs. These data suggest that OECs secrete an OPC mitogen(s) (de Groot et al, 2006;Lipson et al, 2003). The production and survival of oligodendrocytes is regulated by axonal signals (Barres and Raff, 1994;Simons and Trajkovic, 2006;Trapp et al, 1997), and it is therefore possible that the decrease observed in the number of OPCs between Days 16 and 24 in culture was because of the death of OPCs as a result of insufficient axonal signals.…”

Progesterone Attenuates Several Hippocampal Abnormalities of the Wobbler Mouse

“…Therefore, in agreement with previous findings in the spinal cord , progesterone markedly stimulated BDNF mRNA in the hippocampus. This effect may be crucial for some BDNF‐regulated functions of hippocampus, including synaptic transmission, neuronal survival, dendritic spine plasticity and long‐term potentiation . The diminished BDNF mRNA in the hippocampus of untreated Wobblers may be the consequence of the ongoing neurodegeneration.…”

Rat Bone Marrow-Derived Schwann-Like Cells Differentiated by the Optimal Inducers Combination on Microfluidic Chip and Their Functional Performance

“…[2] have previously reported. BDNF has been reported to have a regulation in axon myelination and regeneration, neuronal survival, axonal outgrowth, differentiation and glial cell proliferation [31]–[33]. BDNF is initially elevated before myelination and has been shown to modulated neuron-glia interactions in PNS and CNS [34], [35].…”