Endogenous nerve growth factor is required for regulation of the low affinity neurotrophin receptor (p75) in sympathetic but not sensory ganglia

Abstract

During development, many sympathetic and sensory neurons are dependent on nerve growth factor (NGF) for survival. The low affinity neurotrophin receptor (p75), expressed in these neurons, is regulated by exogenous NGF in vitro and in vivo. However, whether p75 expression in vivo is under the control of endogenous NGF has not been determined. The role of NGF in regulating the expression of p75 in sympathetic and sensory nerves was investigated in Sprague-Dawley rats treated with an antiserum specific for NGF. P75 was differentially regulated. P75 immunoreactivity (-ir) within sympathetic neurons in the superior cervical ganglia (SCG) was reduced after 2 days, and disappeared after 5 days, of treatment with the NGF antiserum. In contrast, a significant increase in p75-ir was detected in nerve bundles within and close to the SCG from 3 to 14 days after treatment. A similar pattern of p75 expression was observed in the stellate and coeliac ganglia. In contrast, p75 expression in nerve terminals of the mesenteric arteries and irides was reduced. However, in the same animals the expression of p75 was not significantly affected by the treatment in dorsal root, trigeminal or nodose ganglia, salivary gland or small intestine. In contrast to p75, the NGF high affinity receptor trkA was little affected in sympathetic neurons by depletion of endogenous NGF for 2 weeks. These results indicate that endogenous NGF is required in sympathetic ganglia for the expression of p75 but not trkA in neurons, but for the down-regulation of p75 in glia. In contrast, endogenous NGF is not essential for the regulation of p75 in neurons or glia within sensory ganglia.

NEURORECEPTOR mRNA EXPRESSION IN THE RAT MESENTERIC ARTERY DEVELOPS INDEPENDENTLY OF INNERVATION

“…The antiserum was raised in sheep against mouse salivary gland NGF. 32 Newborn animals were injected subcutaneously with undiluted sera at 10 ml/g bodyweight, with injections daily from postnatal day 0 to 6. This treatment has been shown previously to cause a complete loss of catecholamine containing ®bres supplying the rat mesenteric artery.…”

Neurotrophic Factors Are Required by Mature Sympathetic Neurons for Survival, Transmission and Connectivity

“…9). 30 Our working hypothesis for this phenomenon is that loss of neurotrophic factors from the periphery (unknown factors different to NGF or NT3) results in up-regulation of GGF by the sensory neurons and, following their release, activation of the satellite glia, leading to increased synthesis of p75, NT3 and NGF. The increased availability of NT3 and NGF in the presence of increased p75 provides a high concentration of neurotrophic factors acting as chemoattractants for the nearby sympathetic nerve terminals.28"' This possibility is being examined.…”

Plasticity in rat uterine sympathetic nerves: the role of TrkA and p75 nerve growth factor receptors

“…1991, 1994; Ma et al. 1992; Zhou & Rush, 1996b), they do show a down‐regulation of the receptor in specific populations of neurons that are vulnerable to age‐related neurodegeneration. If p75 is considered to act cooperatively with TrkA in binding NGF (Hempstead et al.…”

“…An alternative explanation is that reductions in p75 levels could represent a protective response of uterine‐related sympathetic neurons to the NGF deprivation that occurs at late pregnancy. Reductions of p75 have been suggested to contribute to the survival of sympathetic neurons deprived of NGF for short periods of time (Zhou & Rush, 1996b). Further studies, including examination of the impact of altered expression levels on NGF uptake in sympathetic neurons, are required to resolve the functional significance of the changes observed.…”