INTRODUCTION: In mammals, spinal cord transection results in permanent loss of locomotor function. Our previous investigations demonstrated that intraspinal grafting of an embryonic (E14) brainstem raphe area enhances hindlimb locomotor recovery in adult paraplegic rats. This process is mediated mainly through serotonergic (5‑HT) neurons. AIM(S): The aim of the present investigation was to determine the role of catecholaminergic (CA) neurons that are present in the grafted tissue in this recovery. METHOD(S): The experiments were performed on the inbred strain WAG rats after spinal cord total transection. Grafts were placed in the spinal cord below the total transection and included 5-HT neurons derived from the embryonic (E14) brainstem. Two months later, locomotor performance was tested with chronic EMG recordings from Soleus (Sol) and Tibialis Anterior (TA) muscles, allowing quantification of limb movement recovery. After completing the functional testing, the spinal cords were harvested for morphological investigations. RESULTS: In the graft area, besides 5-HT neurons, we found a number of CA neurons of graft origin. The CA innervation, however, was weaker than that of 5-HT and limited to specific areas of the spinal cord. We showed that the 5-HT and CA neurons were fully differentiated at the time of tissue dissection for grafting and that the host environment did not stimulate their proliferation and differentiation. The locomotor abilities of the spinal grafted rats were facilitated by application of Yohimbine and suppressed by Clonidine, likely through their actions on noradrenergic autoreceptors. CONCLUSIONS: Our results indicate a potent role of the CA innervation in locomotor recovery in paraplegic rats. In addition to the important role of 5‑HT neurons in this process, our findings provide new insights into the mechanisms underlying the locomotor recovery in rats. FINANCIAL SUPPORT: This work was supported by ERA-NET NEURON CoFund Consortium NEURONICHE (ERA‑NET‑Neuron/16/17).
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