Expression of brain-derived neurotrophic factor and TrkB neurotrophin receptors after striatal injury in the mouse.
Brain-derived neurotrophic factor (BDNF) promotes the survival and differentiation of nigral dopaminergic neurons and supports the activity of dopaminergic cells grafted into the striatum. However, little attention has been given to the physiological role of endogenous BDNF and its receptor TrkB within the nigrostriatal dopamine system. We know that striatal injury is followed by long-term stimulation of dopaminergic activity in the striatum, could BDNF play a role in this phenomenon? One week after physical injury to the striatum of C57/Black mice, just before dopaminergic activation becomes obvious, in situ hybridization on coronal sections through mouse striatum reveals that BDNF mRNA expression increases significantly before returning to basal levels within 1 month. Expression of mRNA for TrkB follows a very different pattern. No change of expression of the full-length and catalytically competent TrkBTK+ receptor is seen. However, expression of the truncated form of the receptor TrkTK-, which lacks the catalytic tyrosine kinase domain, does increase and stays elevated for at least 2 months after injury. When combined with observations of dopaminergic activation after striatal injury and the neuroprotective effects of BDNF introduced into the striatum, our findings suggest that BDNF and TrkBTK- do indeed play a role in dopaminergic regeneration and repair.
Wong
J Y
JY
Department of Neurology, University of Melbourne, Austin, Australia.
Liberatore
G T
GT
Donnan
G A
GA
Howells
D W
DW
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D003342:Corpus Striatum / Q000293:injuries* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D004298:Dopamine