Biphasic Response of Spinal GABAergic Neurons after a Lumbar Rhizotomy in the Adult Rat

Authors


  • The authors are grateful to Dr A. Tobin for providing the GAD67, rat cDNA. They also thank A. Legrand for technical assistance, J.-R. Teilhac for photographic work, Dr I. Chaudieu for critical comments, M. Anoal for her support and Dr L. Salhi for the correcting the manuscript. This research was funded by the IRME (Institut pour la Recherche sur la Moelle Epinière) and the AFM (Association Françise contre les Myopathies). A. D. is the recipient of an ME fellowship.

A. Dumoulin, as above

Abstract

The expression of γ-aminobutyric acid (GABA) and of the isoforms of the enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified in several rat brain structures in different injury models. The aim of the present work was to determine whether such plasticity of the GABAergic system also occurred in the deafferented adult rat spinal cord, a model where a major reorganization of neural circuits takes place. GABAergic expression following unilateral dorsal rhizotomy was studied by means of non-radioactive in situ hybridization to detect GADs67 mRNA and by immunohistochemistry to detect GAD67 protein and GABA. Three days following rhizotomy the number of GAD67 mRNA-expressing neurons was decreased in the superficial layers of the deafferented horn, while GABA immunostaining of axonal fibres located in this region was highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA-expressing neurons were bilaterally detected in deep dorsal and ventral layers, this expression being correlated with the increased detection of GADs67 immunostained somata and with the reduction of GABA immunostaining of axons. GABA immunostaining was frequently found to be associated with reactive astrocytes that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP) but remained GADs67 negative. These results indicate that degeneration of afferent terminals induces a biphasic response of GABAergic spinal neurons located in the dorsal horn and show that many spinal neurons located in deeper regions re-express GAD67, suggesting a possible participation of the local GABAergic system in the reorganization of disturbed spinal networks.

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