Journal of neurochemistry
-
Journal of neurochemistry · Aug 2010
Selective lesion of the developing central noradrenergic system: short- and long-term effects and reinnervation by noradrenergic-rich tissue grafts.
The possibility to selectively remove noradrenergic neurons in the locus coeruleus/subcoeruleus (LC/SubC) complex by the immunotoxin anti-dopamine-beta-hydroxylase (DBH)-saporin has offered a powerful tool to study the functional role of this projection system. In the present study, the anatomical consequences of selective lesions of the LC/SubC on descending noradrenergic projections during early postnatal development have been investigated following bilateral intraventricular injections of anti-DBH-saporin or 6-hydroxydopamine to immature (4 day old) rats. Administration of increasing doses (0.25-1.0 microg) of the immunotoxin produced, about 5 weeks later, a dose-dependent loss of DBH-immunoreactive neurons in the LC/SubC complex (approximately 45-90%) paralleled by a similar reduction of noradrenergic innervation in the terminal territories in the lumbar spinal cord. ⋯ In these animals, the number of surviving neurons in the grafts and the magnitude of the reinnervation, with fibers extending in both the grey and white matter for considerable distances, were seen higher than those reported in previous studies using adult recipients. This would suggest that the functional interactions between the grafted tissue and the host may recapitulate the events normally occurring during the ontogenesis of the coeruleo-spinal projection system, and can therefore be developmentally regulated. Thus, the neonatal anti-DBH-saporin lesion model, with the possibility to produce graded noradrenergic depletions, holds promises as a most valuable tool to address issues of compensatory reinnervation and functional recovery in the severed CNS as well as to elucidate the mechanisms governing long-distance axon growth from transplanted neural precursors.
-
Journal of neurochemistry · Aug 2010
Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice.
The chemokine fractalkine (FKN) is a critical mediator of spinal neuronal-microglial communication in chronic pain. Mature FKN is enzymatically cleaved from neuronal membranes and activation of its receptor, CX3CR1, which is expressed by microglia, induces phosphorylation of p38 MAPK. We used CX3CR1 knockout (KO) mice to examine pain behaviour in the absence of FKN signalling. ⋯ In WT mice, inflammation and nerve injury increased spinal cord CX3CR1 and FKN expression. FKN protein was also increased in KO mice following inflammation but not after neuropathy, suggesting the FKN/CX3CR1 system is differently affected in the two pain models. Loss of FKN/CX3CR1 neuroimmune communication attenuates hyperalgesia and allodynia in a modality-dependent fashion highlighting the complex nature of microglial response in pathological pain models.