Expression of neurotransmitter genes in rat spinal motoneurons after chemodenervation with botulinum toxin

Botulinum toxin is widely used for the treatment of focal movement disorders, where chemodenervation is used to decrease hyperactivity in selected muscles. Beside a focal paresis, widespread effects on neuromuscular synaptic function have been demonstrated. However, reactions of motoneurons after neuromuscular chemodenervation without gross morphological lesions are largely unknown. Peripheral axotomy, in contrast, leads to profound changes in the expression of several genes, including those encoding neurotransmitters, in motoneurons. We therefore examined the expression of neurotransmitter genes in rat motoneurons six days after intramuscular botulinum toxin application in the right gastrocnemius muscle. Similar doses of botulinum toxin as used in human where injected. A focal bilateral increase in expression of the choline acetyltransferase gene and a widespread bilateral increase of the beta-calcitonin-gene-related peptide and the enkephalin genes was measured in motoneurons after botulinum toxin injection. Cholecystokinin had a lower expression after botulinum toxin injections. Growth-associated protein 43, nitric oxide synthase, somatostatin and proopiomelanocortin messenger RNA were not found in motoneurons of both groups. Our results demonstrate that changes in the expression of neurotransmitter genes in motoneurons also occur after chemodenervation but with different patterns to those found after mechanical nerve lesioning. These changes reflect focal and widespread modulative events. The knowledge of these events should lead to a better understanding of the focal paralysis and of the more widespread effects found in human after intramuscular injection of botulinum toxin.