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

Abstract

1. Two neuronal growth factors, nerve growth factor (NGF) and neurotrophin 3 (NT3), have been studied for their action on the developing and mature sympathetic nervous system. 2. Antibodies to each factor have proved useful as reagents for the detection and quantification of NGF and NT3. They have also proved valuable in uncovering the functional roles of each factor by their ability to neutralize the endogenous molecules. 3. Nerve growth factor acts on postnatal neurons to control neurotransmission, connectivity and survival. Like NGF, NT3 is synthesized by effector tissues and is retrogradely transported by post-ganglionic neurons to prevent cell death. However, the two factors have been shown to have quite distinct functions in mature neurons, indicating the existence of different signalling pathways. This differential action extends to secondary influences on satellite glia. 4. Pathological consequences result from excessive growth factor synthesis leading, in the hypertensive rat, to hyperinnervation and elevated blood pressure. Satellite glial cell synthesis of the factors and their receptors following peripheral nerve damage appears to be responsible for the establishment of inappropriate neuronal connections between sympathetic nerve terminals and sensory somata. 5. It is concluded that these potent factors control, by both coincident and independent mechanisms, sympathetic neuronal function throughout the life of the animal.

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males

“…These results are consistent with the data on elevated NGF in SHR in vivo, and with the hypothesis of altered feedback regulation (Rush et al 1997).…”

“…This idea suggests that NGF output by smooth muscle is controlled by factors secreted from sympathetic nerve terminals, such as noradrenaline. Partial support of this notion derives from experiments in which denervation of mesenteric arteries leads to decreased NGF mRNA, while antibodies against NGF caused elevated NGF levels (Rush, 1997). This hypothesis predicts that the control mechanism for NGF production is significantly altered in the SHR, allowing excess NGF to be expressed.…”

“…Therefore, a disturbed genetic component of the hypertensive rat genome, associated with the regulation of smooth muscle NGF output, may contribute to elevated bladder smooth muscle NGF content and ultimately neurogenic changes in the control of voiding frequency. Rush (1997) has proposed in a recent review that there may be a negative feedback control system on the synthesis and/or release of NGF. This idea suggests that NGF output by smooth muscle is controlled by factors secreted from sympathetic nerve terminals, such as noradrenaline.…”

Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input

“…NGF is essential for the survival of sympathetic neurons during development (Gorin and Johnson 1980;Crowley et al 1994) as well as in adulthood (Ruit et al 1990;Ghasemlou et al 2004). NT-3 also is important for the survival of sympathetic neurons (Zhou and Rush 1995;Rush et al 1997;Francis et al 1999). Severe deficits in sensory and sympathetic neuronal populations have been demonstrated in NT-3 null mutant mice (Farinas et al 1994).…”

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats

“…In particular, alterations in the content of neurotrophin nerve growth factor (NGF) in tissues (skin, muscle and serum) [3] are associated with spinal variations in substance P (SP) [3] and transient receptor potential vanilloid 1 (TRPV1) receptor [4,5]. These latter are known to be under the control of NGF [6][7][8] and have been related to diabetes-induced neuropathy. Diabetic neuropathy could benefit from NGF-based therapies [9], but the clinical use of NGF has been hampered by the development of important side effects, such as hyperalgesia, pain and autonomic dysfunctions [10].…”