The endogenous survival promotion of axotomized rat corticospinal neurons by brain-derived neurotrophic factor is mediated via paracrine, rather than autocrine mechanisms.
The previously reported rescue of corticospinal neurons (CSN) from axotomy-induced death by intracortical glial cell line-derived neurotrophic factor (GDNF)- and neurotrophin-3 (NT-3)-infusions depends on endogenous cortical brain-derived neurotrophic factor (BDNF). The present study examines whether BDNF, GDNF, or NT-3 can stimulate an autocrine or paracrine BDNF-support of lesioned CSN. BDNF-infusions increase BDNF mRNA-expression throughout cortical layers 2-5 and NT-3-treatment results in upregulation of BDNF-transcripts in the upper cortical layers. In contrast, GDNF-treatment had no effect. While virtually all CSN express the BDNF-receptor trkB, less than half of them express BDNF, and these expression patterns are unchanged after axotomy and the different neurotrophic factor treatments. The findings suggest that axotomized CSN are supported via a paracrine BDNF-mechanism which can be stimulated by BDNF- and NT-3-, but not by GDNF.
Schütte
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A
Department of Anatomy, University of Saarland, D-66421 Homburg/, Saar, Germany.
Yan
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Q
Mestres
P
P
Giehl
K M
KM
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D019771:Axotomy / Q000009:adverse effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003714:Denervation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020933:Neurotrophin 3 / Q000378:metabolism / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3