Increased Expression of BDNF and trkB mRNA in Rat Facial Motoneurons after Axotomy

Abstract

Motoneurons of the adult survive after axotomy even though they are deprived of putative target derived trophic factors. Alternative sources of trophic support may substitute. In this study we test the hypothesis that the immediate environment of the motoneuronal cell body or the cell body itself increases the production of trophic factors after axonal injury. Using in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), we report that after axotomy, rat facial motoneurons increase the expression of mRNA for brain-derived neurotrophic factor (BDNF) and its receptor trkB. After transection of the facial nerve, we measured a 2- to 4-fold increase in BDNF mRNA expression which had its onset between 3 and 8 h after injury. The BDNF mRNA levels peaked at approximately 1-2 days and gradually declined thereafter to return to contralateral levels within 7 days of injury. Western blotting revealed a several-fold increase in BDNF as early as 24 h, which subsequently reached a maximum in approximately 5-7 days and was still sustained at 2 weeks post-axotomy. Using exon-specific primers, we determined that the increase in BDNF mRNA is largely due to an increased expression from the promoters of exons IV and III, and to a lesser extent from exons I and II. Analysing the mRNA expression for the BDNF receptor, trkB, we found a 2- to 3-fold increase in full-length trkB mRNA expression starting 2 days after axotomy which lasted 2-3 weeks. These findings suggest that BDNF might act locally on axotomized motoneurons in an autocrine fashion, providing support for axotomized motoneurons during the first weeks after axotomy.

Long-Term Adeno-Associated Viral Vector-Mediated Expression of Truncated TrkB in the Adult Rat Facial Nucleus Results in Motor Neuron Degeneration

“…Downregulation of marker expression in TrkB.T1-expressing motor neurons GFP-TrkB.T1 was expressed on soma, dendrites, and axons. Overexpression of TrkB.T1 likely results in a blockade of targetderived NT-4/5 , locally produced BDNF (Kobayashi et al, 1996), and BDNF anterogradely transported from other sources (Fawcett et al, 1998). TrkB ligands regulate axonal and dendritic development and synaptic plasticity (for review, see McAllister et al, 1999;Schinder and Poo, 2000).…”

Facial nerve injuries cause changes in central nervous system microglial cells

“…Se sabe que después de las lesiones de nervio periférico, las motoneuronas cuyos axones han sido lesionados sufren cambios que incluyen la retracción de su árbol dendrítico (10,11), la modificación de sus propiedades electrofisiológicas (tanto activas como pasivas) (12)(13)(14) y cambios en los niveles de expresión de determinados genes (15)(16)(17)(18).…”

Retracción a largo plazo del árbol dendrítico de neuronas piramidales córtico-faciales por lesiones periféricas del nervio facial

“…Al ser privadas de sus dianas sinápticas tras lesiones de nervio periférico, las motoneuronas de animales adultos entran en un programa de regeneración que incluye retracción de sus arborizaciones dendríticas (25,26), incremento en la expresión de diversas proteínas, como BDNF (Brain Derived Neurotrophic Factor) (27), c-Fos y c-Jun (28), y cambios en las propiedades electrofisiológicas pasivas y activas (29)(30)(31).…”