Elsevier

Neuroscience

Volume 100, Issue 1, 7 September 2000, Pages 171-181
Neuroscience

Exogenous brain-derived neurotrophic factor regulates the synaptic composition of axonally lesioned and normal adult rat motoneurons

https://doi.org/10.1016/S0306-4522(00)00256-6Get rights and content

Abstract

Brain-derived neurotrophic factor has previously been shown to promote survival and axonal regeneration in injured spinal motoneurons and, also, to modulate synaptic transmission and regulate the density of synaptic innervation in a variety of neurons. The present light and electron microscopic study demonstrates synaptotrophic effects of exogenously applied brain-derived neurotrophic factor on the synaptic composition of both normal and axonally lesioned adult rat spinal motoneurons. After L5–L6 ventral root avulsion, a massive loss of all types of boutons occurred on the somata of the lesioned motoneurons which persisted for at least 12 weeks postoperatively. We found that (i) intrathecal infusion of brain-derived neurotrophic factor during the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restored synaptic covering and significantly reduced microglial reaction; (iii) the synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported F-type boutons with presumably inhibitory function, while it had little effect on S-type boutons associated with excitatory action; and (v) in normal unlesioned motoneurons, four weeks of treatment with brain-derived neurotrophic factor induced sprouting of F-type boutons, a loss of S-type boutons and motoneuron atrophy.

The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly influence the synaptic composition in normal motoneurons.

Section snippets

Experimental procedures

The animal care and experimental procedures were carried out according to the standards established by the NIH Guide for Care and Use of Laboratory Animals (NIH publications No. 86-23, revised 1985) and the European Communities Council Directive (86/609/EEC). This study was also approved by the Northern Swedish Committee for Ethics in Animal Experiments.

The experiments were performed on 84 adult (180–200 g, eight to 10 weeks old) female Sprague–Dawley rats (Møllegaard Breeding Centre, Denmark)

Synaptological features of normal motoneurons

In normal unoperated rats, an intense and distinct presynaptic SYN labelling was observed around the somata and proximal dendrites of the motoneurons, while the ventral horn neuropil displayed a more diffuse and homogeneous staining pattern (Fig. 1A). Electron microscopically, the majority of synaptic terminals on the motoneuron somata was of the F-type (64.5%), while the S- and C-type boutons represented 31.9% and 3.2%, respectively. The M-type boutons were only occasionally observed on the

Discussion

The motoneurons of the lumbar spinal cord were chosen as experimental model, since the normal synaptology of these cells is known in considerable detail in both rat3 and cat.13., 14., 15., 34. The present results show that BDNF not only promotes cell survival and axon regeneration in axonally lesioned spinal motoneurons,57., 62., 67. but also influences the organization of synaptic inputs in both normal and lesioned motoneurons Although BDNF did not prevent the initial synaptic stripping after

Conclusions

The present results indicate that in addition to restorative effects on the synaptology of axonally lesioned motoneurons, BDNF induces a reorganization of the synaptic circuitry of normal uninjured neurons. Therefore, in attempts to design strategies using neurotrophins in the treatment of neuronal injuries, interest should be focused not only on the beneficial effects on the lesioned pathways, but also on possible adverse effects on intact neuronal systems.

Acknowledgements

This study was supported by the Swedish Medical Research Council (project 02886), International Institute for Research in Paraplegia, Umeå University, County of Västerbotten, Gunvor and Josef Anér’s Foundation, Swedish Society for Medical Research and J. C. Kempe Foundation. We thank Mrs G. Folkesson and Mrs A. Berglund for technical assistance and Regeneron Pharmaceuticals, Inc., for generously supplying us with BDNF.

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