The endogenous survival promotion of axotomized rat corticospinal neurons by brain-derived neurotrophic factor is mediated via paracrine, rather thanautocrine 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 whethe r BDNF, GDNF, or NT-3 can stimulate an autocrine or paracrine BDNF-support of lesioned CSN. BDNF-infusions increase BDNF mRNA-expression throughout co rtical layers 2-5 and NT-3-treatment results in upregulation of BDNF-transc ripts in the upper cortical layers. In contrast, GDNF-treatment had no effe ct. While virtually all CSN express the BDNF-receptor trkB, less than half of them express BDNF, and these expression patterns are unchanged after axo tomy 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, (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.