Rat astrocytes and Schwann cells in culture synthesize nerve growth factor-like neurite-promoting factors

228

114

A key role has not yet been identified for (3 nerve growth factor (NGF) in the growth responses that continue to be expressed in the sensory neurons of adult animals. We have now examined the effects ofdaily administration to adult rats (and in a few experiments, mice) of antiserum to NGF on (i) the collateral sprouting of undamaged nociceptive nerves that occurs into denervated adjacent skin and (ii) the regeneration of cutaneous sensory axons that occurs after they are damaged. The results were unexpected. All collateral sprouting was prevented and that already in progress was halted; sprouting resumed when treatment was discontinued. In contrast, the reestablishment, and even enlargement, ofcutaneous nerve fields by regenerating axons was unaffected by anti-NGF treatment, even after dorsal rhizotomy was done to eliminate any central trophic support. In denervated skin, regenerating and collaterally sprouting axons utilized the same cellular pathways to establish functionally identical fields, thus displaying apparently identical growth behaviors, yet anti-NGF treatment clearly distinguished between them. We suggest that endogenous NGF is responsible for the collateral sprouting of nociceptive axons, probably reflecting an ongoing function of NGF in the regulation of their fields. This demonstration in the adult sensory system of a defined role for NGF in nerve growth could apply to nerve growth factors generally in the adult nervous system. The regeneration, however, ofnociceptive axons (and nonnociceptive ones) is not dependent on NGF.Although /3 nerve growth factor (NGF) is essential for the development and survival of neuronal populations in the autonomic and sensory nervous systems (1-4), by birth or shortly thereafter, sensory neurons will survive largely independent of it (1, 5). Nevertheless in adult animals NGF continues to be synthesized in peripheral target tissues (6, 7), sensory axons can take up and transport it retrogradely (8, 9), while maintained NGF deprivation leads to a lowering ofboth substance P levels (10), and even neuronal cell size (11), in dorsal root ganglia. Significantly, two striking growth behaviors of sensory neurons also continue to be demonstrable in adult animals: these are axonal elongation and collateral sprouting. There are more than morphological distinctions between these two. Whereas collateral sprouting, both during development and later, is a characteristic of normal undamaged nerves, and is essentially confined to target tissues (12, 13), elongation is seen in adults particularly in the form of regeneration of an axon after peripheral nerve damage. In adult mammals, large myelinated mechanosensory axons readily regenerate after they are crushed, but unlike both myelinated (14) and unmyelinated (15) In the present study we compared the effects of anti-NGF treatment on collateral sprouting and axonal regeneration of cutaneous nociceptive nerves in adult rats. Surprisingly, though the cutaneous pathways normally followed by each were identical, sprouting was p...

Section: Discussionmentioning

confidence: 99%

Evidence that endogenous beta nerve growth factor is responsible for the collateral sprouting, but not the regeneration, of nociceptive axons in adult rats.

Diamond¹,

Coughlin²,

Macintyre³

et al. 1987

228

114

“…Results (6) and after peripheral nerve injury in vivo (7,8). The NGF receptor has been reported to be present in the rat retina during development (19).…”

Section: Resultsmentioning

confidence: 99%

“…In those experiments, an average of 19% with a maximum of 20% surviving RGCs was found 7 weeks after optic nerve section, whereas in the present experiment, an average of 22.5% with a peak of 44% surviving RGCs was determined for longer times of survival (9 weeks (20), or via the production of extracellular matrix components (21,22), a suitable substrate for neurite outgrowth in vitro. SCs are also known to produce other still-undetermined neuronotrophic factors (6), which could play a role in the survival of axotomized RGCs.…”

Section: Resultsmentioning

confidence: 99%

“…The positive effect of SCs on regeneration and survival of injured neurons is believed to be due to the production of supportive or neuronotrophic molecules, or both. For instance, there is evidence indicating that SCs produce nerve growth factor (NGF) or a NGF-like protein in vitro (6) and after peripheral nerve injury in vivo (7,8). Recently, it has been shown that repetitive intraocular injections of NGF enhance the survival of axotomized rat RGCs (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Schwann cells promote the survival of rat retinal ganglion cells after optic nerve section.

Maffei

Carmignoto

Perry

et al. 1990

Schwann cells (SCs) are known to play an important role for the regeneration of mammalian peripheral nerves. Their effect is likely due to the production of neuronotrophic and/or supportive factors. Here we study the effect of intraocular transplant of SCs on the survival of rat retinal ganglion cells (RGCs) after the intracranial section of the optic nerve. SCs were injected intraocularly in adult hooded rats. Surviving RGCs were retrogradely labeled with horseradish peroxidase applied to the proximal stump of the optic nerve. Results show that intraocular transplants of SCs promote the survival of a large number ofRGCs for periods as long as 9 and 14 weeks after optic nerve section. In experimental retinae, surviving RGCs were 2-to 8-fold more numerous than in controls. This finding suggests that SCs are the source of factors that promote the survival ofRGCs. Nerve growth factor is produced by SCs, and the intraocular injection of nerve growth factor has been previously shown to promote RGC survival. The rescuing effect of SCs on RGCs is greater than that obtained by intraocular injection of nerve growth factor. This greater effect may be due to the action of other neurotrophic factors produced by SCs or by transplanted SCs producing NGF in a sustained fashion.The limited capacity of central nervous system (CNS) neurons to regenerate is thought to be due in part to the presence of nonpermissive factors such as myelin-producing oligodendrocytes (1) or to the absence of neurotrophic factors, or to both (2). In the peripheral nervous system, where regeneration takes place, Schwann cells (SCs) play an important role in promoting regeneration (3). To some extent they also can promote regeneration of CNS neurons. A peripheral nerve segment grafted to the optic nerve promotes partial survival and regeneration of rat retinal ganglion cells (RGCs) (4). This effect is supposed to be due to nonneuronal cells, presumably SCs, present in the graft (4, 5). The positive effect of SCs on regeneration and survival of injured neurons is believed to be due to the production of supportive or neuronotrophic molecules, or both. For instance, there is evidence indicating that SCs produce nerve growth factor (NGF) or a NGF-like protein in vitro (6) and after peripheral nerve injury in vivo (7,8). Recently, it has been shown that repetitive intraocular injections of NGF enhance the survival of axotomized rat RGCs (9). In the present study we test the hypothesis that intraocular transplant of SCs promotes the survival of rat RGCs after axotomy.Our results show that SCs are dramatically effective in rescuing RGCs from degeneration. Whereas in control retinae only 5% of the total population of RGCs survive 9 weeks after optic nerve section, in experimental retinae survival of RGCs was enhanced 2-to 8-fold. In experimental retinae RGCs also display a normal soma size. Hamilton syringe. The tip of the needle was inserted under microscopic guidance through the dorsal limbus of the eye. The injection was performed several days before...

“…Nevertheless, it is possible that the contribution of glial cells is important both in vivo and in vitro. There is evidence that p-NGF is produced by glial cells (34). In vivo, neural damage results in reactive gliosis, a phenomenon that may contribute to increased availability of endogenous trophic factors.…”

Section: Methodsmentioning

confidence: 99%

Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons.

Cuello

Garofalo

Kenigsberg

et al. 1989

150

The effects of nerve growth factor (3(-NGF) and ganglioside GM1 on forebrain cholinergic neurons were examined in vivo and in vitro. Following unilateral decortication of rats, GM1 (5 mg/kg per day) administered intracerebroventricularly could protect forebrain cholinergic neurons of the nucleus basalis magnocellularis from retrograde degeneration in a manner comparable to P-NGF. Administered in combination with (-NGF, GM1 produced a significant increase in choline acetyltransferase activity in the nucleus basalis magnocellularis and remaining cortex ipsilateral to the lesion. Concentrations of GM1 that were ineffective when administered alone in this lesion model, when given with .3-NGF, potentiated (i-NGF effects in both of the above brain areas. In dissociated septal cells in vitro, an increase in choline acetyltransferase activity was noted at fi-NGF concentrations as low as 0