Intraspinal noradrenergic-rich implants reverse the increase of alpha 1 adrenoceptors densities caused by complete spinal cord transection or selective chemical denervation: a quantitative autoradiographic study.
This study examined, in the adult rat, whether the intraspinal transplantation of a cell suspension of embryonic day (ED)13 rat locus coeruleus primordia was able to normalize the lesion-induced increase of spinal alpha 1-adrenoceptors. Two experimental models of spinal denervation were studied. The first model consisted of a complete spinal cord transection (thoracic vertebrae level T8-T9) and 1 week later, the cell suspension was transplanted below the section; the second one was obtained by a selective chemical lesion of the noradrenergic (NA) system and one month later, the cell suspension was implanted at the same level as in transected rats. Five weeks after grafting, all animals were sacrificed and spinal cord tissue sections were processed for immunohistochemical detection of noradrenaline or for quantification of alpha 1-adrenoceptors binding sites densities using [3H]prazosin as a ligand. After 6-OHDA lesion, as well as caudally to the transection, a significant increase by 21% (P < 0.01) to 68% (P < 0.001) of alpha 1-adrenoceptors densities was detected. The implantation of embryonic NA neurons into the denervated spinal cord led to a reversal of the lesion-induced increase of spinal alpha 1-adrenoceptors, five weeks later. Moreover, this reversal seems to be more effective after mechanical than after chemical denervation.
Roudet
C
C
INSERM U.318, LAPSEN, Département des Neurosciences Cliniques et Biologiques, Grenoble, France.
Giménez y Ribotta
M
M
Privat
A
A
Feuerstein
C
C
Savasta
M
M
D000818:Animals; D001345:Autoradiography; D016380:Brain Tissue Transplantation / Q000502:physiology*; D017690:Cell Transplantation / Q000502:physiology*; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000637:transplantation*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine; D011224:Prazosin; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*; D013563:Sympathectomy, Chemical
D018340:Receptors, Adrenergic, alpha-1; D016627:Oxidopamine; D009638:Norepinephrine; D011224:Prazosin