Release properties and functional integration of noradrenergic-rich tissue grafted to the denervated spinal cord of the adult rat.
Noradrenaline- (NA-) containing grafts of central (embryonic locus coeruleus, LC) or peripheral (juvenile adrenal medullary, AM, autologous superior cervical ganglionic, SCG) tissue were implanted unilaterally into rat lumbar spinal cord previously depleted of its NA content by 6-hydroxydopamine (6-OHDA) intraventricularly. A microdialysis probe was implanted in the spinal cord 3-4 months after transplantation, and extracellular levels of noradrenaline were monitored in freely moving animals during basal conditions and following administration of pharmacological or behavioural stimuli. Age-matched normal and lesioned animals both served as controls. Morphometric analyses were carried out on horizontal spinal sections processed for dopamine-beta-hydroxylase (DBH) immunocitochemistry, in order to assess lesion- or graft-induced changes in the density of spinal noradrenergic innervation, relative to the normal patterns. In lesioned animals, the entire spinal cord was virtually devoid of DBH-positive fibers, resulting in a dramatic 88% reduction in baseline NA, compared with that in controls, which did not change in response to the various stimuli. LC and SCG grafts reinstated approximately 80% and 50% of normal innervation density, respectively, but they differed strikingly in their release ability. Thus, LC grafts restored baseline NA levels up to 60% of those in controls, and responded with significantly increased NA release to KCl-induced depolarization, neuronal uptake blockade and handling. In contrast, very low NA levels and only poor and inconsistent responses to the various stimuli were observed in the SCG-grafted animals. In AM-grafted animals, spinal extracellular NA levels were restored up to 45% of those in controls, probably as a result of nonsynaptic, endocrine-like release, as grafted AM cells retained the chromaffine phenotype, showed no detectable fibre outgrowth and did not respond to any of the pharmacological or behavioural challenges. Thus, both a regulated, impulse-dependent, and a diffuse, paracrine-like, NA outflow may play roles in the recovery of lesion-induced sensory and/or motor impairments previously reported with these types of grafts following transplantation into the severed spinal cord.
Leanza
G
G
Department of Physiological Sciences, University of Catania, Italy. gileanza@mbox.unict.it
Cataudella
T
T
Dimauro
R
R
Monaco
S
S
Stanzani
S
S
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016380:Brain Tissue Transplantation; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival / Q000502:physiology; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D008125:Locus Coeruleus / Q000637:transplantation*; D017551:Microdialysis; D009412:Nerve Fibers / Q000201:enzymology; D009638:Norepinephrine / Q000032:analysis / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology / Q000601:surgery; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery; D017783:Superior Cervical Ganglion / Q000637:transplantation*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C034674:5-hydroxyindomethacin; D011189:Potassium Chloride; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine; D007213:Indomethacin