Regional-specific regulation of BDNF and trkB correlates with nigral dopaminergic cell sprouting following unilateral nigrostriatal axotomy.

Abstract:

:Axotomy is a powerful stimulus of axon growth and plastic changes. We investigated the potential role of BDNF/trkB signaling in the sprouting of dopaminergic nigral axons in response to axotomy of the medial forebrain bundle. Tyrosine hydroxylase immunohistochemistry revealed the existence of sprouting mechanisms in the axotomized substantia nigra (SN). Time-course changes of trkB mRNA expression demonstrated a robust increase in an area projecting from the rostral tip of the SN to the glial scar, which coincided with evidence of nigral dopaminergic sprouting. In addition, we found an early loss of this messenger in areas related to the knife cut, which recovered by 7 days postlesion. TrkB down-regulation appeared to be associated to the lesion-induced local damage, as it was restricted to an area showing Fluoro-Jade B- and TUNEL positive cells. In trkB-depleted areas, an inverse correlation between mRNA expressions of BDNF and trkB was apparent. Specific induction of BDNF mRNA was mostly seen in border of areas devoid of trkB mRNA. In contrast, in the areas exhibiting trkB mRNA expression, no BDNF mRNA was detected. We suggest that trkB levels could be a determinant element in regulating BDNF expression. Finally, the search for molecules involved in either promoting or inhibiting axonal growth, demonstrated up-regulation of GAP-43 and Nogo-A mRNA at sites close to the knife transections as early as 1 day postlesion. However, overall, Nogo-A induction was more robust than that seen for GAP-43.

journal_name

J Neurosci Res

authors

García Navia JT,Burguillos MA,Ramón-Cueto A,Machado A,Cano J,Venero JL

doi

10.1002/jnr.21654

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

2016-27

issue

9

eissn

0360-4012

issn

1097-4547

journal_volume

86

pub_type

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