The biological responses of axotomized adult motoneurons to brain- derived neurotrophic factor

Abstract

Recent studies showed that brain-derived neurotrophic factor (BDNF) prevents developing motoneurons from naturally occurring and axotomy-induced cell death. Here we examined whether adult motoneurons retain responsiveness to BDNF. Consistent with previous studies, we found that adult spinal and brainstem motoneurons expressed the mRNA of BDNF receptor, trkB. In addition, the trkB immunoreactivities were readily detected in the adult spinal and brainstem motoneurons. We then demonstrated that axotomized adult motoneurons responded to exogenous BDNF. BDNF administered locally markedly attenuated the lesion-induced decrease of ChAT immunoreactivity and activity and enhanced the lesion-induced reexpression of low-affinity NGF receptor immunoreactivity in adult facial motoneurons. Furthermore, we found BDNF administered subcutaneously, intravenously, and into the cerebral ventricle attenuated the lesion-induced decrease of ChAT immunoreactivity in adult facial motoneurons in a dose-dependent fashion. Our data indicate that adult motoneurons retain their responsiveness to BDNF, suggesting that BDNF may be useful as a therapeutic agent for adult motoneuron disease.

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

“…Loss of cholinergic phenotype of axotomized mature motor neurons and rescue thereof by exogenous TrkB ligands is well documented (Yan et al, 1994;Friedman et al, 1995;Wang et al, 1997;Fernandes et al, 1998). Loss of NeuN expression occurs in axotomized facial motor neurons but not in axotomized rubrospinal neurons (McPhail et al, 2004a).…”

“…Cholinergic marker expression in injured adult motor neurons is regulated by exogenously applied TrkB ligands (Yan et al, 1994;Friedman et al, 1995;Tuszynski et al, 1996;Wang et al, 1997;Fernandes et al, 1998). To determine whether overexpression of TrkB isoforms affected the expression of neuronal markers in mature facial motor neurons, we stained sections of AAVinjected animals with an antibody for NeuN, a nuclear protein with DNA binding properties (Mullen et al, 1992), and an antibody for the neurotransmitter synthesizing enzyme ChAT.…”

“…NT-4/5 is the predominant neurotrophin expressed in the targets of mature facial and spinal motor neurons Funakoshi et al, 1995;Griesbeck et al, 1995). Adult motor neurons remain responsive to BDNF, because exogenously applied TrkB ligands maintain the cholinergic phenotype of axotomized adult facial, spinal, and hypoglossal motor neurons (Yan et al, 1994;Friedman et al, 1995;Tuszynski et al, 1996;Wang et al, 1997;Fernandes et al, 1998) and rescue avulsed motor neurons from injury-induced cell death Kishino et al, 1997;Novikov et al, 1997).…”

Neurosteroid regulation of central nervous system development

“…The effects of BDNF on various markers of spinal cord injury and repair are similar to those elicited by treatment with progesterone. These include increased choline acetyl transferase in motoneurons (Yan et al, 1994), increased expression of GAP-43 (Kobayashi et al, 1997) and increased myelin-basic protein (Ikeda et al, 2002). Neurotrophic factors and their receptors are present in developing and in adult spinal cord neurons (Buck et al, 2000;Dreyfus et al, 1999;Schober et al, 1999) suggesting they may play a role in development and in neuronal survival and axonal regeneration (Sayer et al, 2002;Thoenen, 1995).…”

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).…”