Differential Expression of the p75 Nerve Growth Factor Receptor in Glia and Neurons of the Rat Dorsal Root Ganglia after Peripheral Nerve Transection

Abstract

Sympathetic nerve terminals on blood vessels within the dorsal root ganglia sprout after sciatic nerve lesions in the rat. The mechanism underlying this phenomenon is not clear, but might be predicted to involve nerve growth factor or its homologs because these factors are known to trigger collateral sprouting of undamaged sympathetic noradrenergic terminals. We have found that sciatic nerve lesions lead to a decreased expression of neuronal p75, the low-affinity receptor for the neurotrophins, but an increased expression of glial p75 in ipsilateral dorsal root ganglia. Intriguingly, the increased expression of p75 was found primarily in association with glia surrounding large-diameter neurons, which are those associated with the noradrenergic sprouts. A smaller but significant glial response was also found in contralateral ganglia. The glial response in ipsilateral ganglia could be mimicked by ventral, but not dorsal, root transection. The dorsal root lesion-induced glial responses in contralateral ganglia were greater than those induced by ventral root or sciatic nerve lesions. Combined lesions of dorsal root and either ventral root or sciatic nerve did not prevent the glial responses of ipsilateral ganglia, suggesting that a peripheral signal is involved. Colocalization studies indicate that tyrosine hydroxylase-immunoreactive nerve sprouts were associated with p75-immunoreactive glial cells. Thus, increased glial synthesis of p75 might provide an explanation for the abnormal growth of sympathetic fibers in dorsal root ganglia after peripheral nerve injury.

Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury

“…1C,D). The percentages of p75NTR mRNA-positive neurons in the present study are much lower than those previously reported (50 -60%) (Zhou et al, 1996;Bergman et al, 1999). This discrepancy may be attributable to the differences in the criterion used to distinguish between positively and negatively labeled neurons.…”

ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration

“…The reduction in the response of neurons to these inhibitory cues after peripheral nerve injury could be attributable to a modification or downregulation in the receptors that comprise the Nogo receptor complex. Expression of p75 in DRG neurons is downregulated after peripheral injury (Krekoski et al, 1996;Zhou et al, 1996) modification of downstream signal transduction paths or other effectors that lead to growth cone collapse may also contribute (Lehmann et al, 1999;Dergham et al, 2002;Sivasankaran et al, 2004;Spencer and Filbin, 2004;Domeniconi et al, 2005;Koprivica et al, 2005). The conditioning effect contributes therefore, both to an enhancement of axonal growth and a diminished response to myelin inhibitory signals.…”

Satellite glial cells in sensory ganglia: from form to function

“…Other studies showed that after axotomy SGCs proliferated and expressed high levels of neurotrophins (NTs) and the low affinity NT receptor p75 [193]. Interestingly, this increase was localized in SGCs around sensory neurons that innervate the skin, but not those innervating the muscle [74].…”