Brain‐derived neurotrophic factor (BDNF) mediates bone morphogenetic protein‐2 (BMP‐2) effects on cultured striatal neurones

Abstract

Bone morphogenetic proteins are members of the transforming growth factor-b superfamily that have multiple functions in the developing nervous system. One of them, bone morphogenetic protein-2 (BMP-2), promotes the differentiation of cultured striatal neurones, enhancing dendrite growth and calbindin-positive phenotype. Bone morphogenetic proteins have been implicated in cooperative interactions with other neurotrophic factors. Here we examined whether the effects of BMP-2 on cultured striatal neurones are mediated or enhanced by other neurotrophic factors. BMP-2 had a cooperative effect with low doses of brain-derived neurotrophic factor or neurotrophin-3 (but not with other neurotrophic factors such as glial cell line-derived neurotrophic factor, neurturin or transforming growth factor-b2) on the number of calbindin-positive striatal neurones. Moreover, BMP-2 induced phosphorylated Trk immunoreactivity in cultured striatal neurones, suggesting that neurotrophins are involved in BMP-2 neurotrophic effects. The addition of TrkB-IgG or antibodies against brain-derived neurotrophic factor abolished the effects of BMP-2 on the number and degree of differentiation of calbindin-positive striatal neurones. Indeed, BMP-2 treatment increased brain-derived neurotrophic factor protein levels in treated cultures media and BDNF immunocytochemistry revealed that this neurotrophin was produced by neuronal cells. Taken together, these results indicate that brain-derived neurotrophic factor mediates the effects of BMP-2 on striatal neurones.

BMPR1a Signaling Determines Numbers of Oligodendrocytes and Calbindin-Expressing Interneurons in the Cortex

“…In contrast, studies by another group found that BMP treatment of cultured striatal cells increased the number of calbindinpositive interneurons, although this effect appeared to be an indirect one mediated by astrocytes and other growth factors (Gratacos et al, 2001(Gratacos et al, , 2002. In our study, null mutation of BMPR1a did not alter the total number of interneurons in the telencephalon, although there was a trend toward an increase.…”

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

“…Primary neurons from striatum were cultured from E18 CD-1 mice embryos as previously described (Gratacos et al, 2001). In brief, the dissected striatum was treated with 1.25% trypsin (Sigma-Aldrich) for 10 min before being mechanically dissociated with a flame polished Pasteur pipette.…”

Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation

“…However, BMP4 expression peaks in the cortex around the same time as BDNF, suggesting that BMP4 and BDNF might cooperate in the differentiation of the PV + interneurons in the cortex. Similar cooperative effects between BMPs and BDNF have been reported for other cell populations in the brain, and some of the effects of BMPs may have been mediated through BDNF (Galter et al, 1999;Gratacos et al, 2001). Unlike BDNF, little is known about the effects of BMP4 signaling on synaptic plasticity, or whether BMP4 expression is regulated by synaptic activity, although recently BMP signaling was implicated in enhancing synaptic plasticity in the hippocampus (Sun et al, 2007).…”