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G Raivich

Publications and source records attributed to G Raivich.

60 records · Page 4Linked to original sources

Nerve growth factor (NGF) receptor expression in chicken cranial development.

In order to map the expression of receptors for nerve growth factor (NGF) during brain and cranial ganglia development, iodinated NGF (125I beta NGF) was used as a probe in an autoradiographical analysis performed between embryonic day 3 (E3) and posthatching day 3 (P3) of chicken development. Heavy autoradiographic labelling was observed at the classical NGF target sites, the proximal cranial sensory ganglia and the sympathetic superior cervical ganglion, throughout development and after hatching. In contrast, only weak labelling could be detected during a restricted time span in the vestibulocochlear (E4-E8) and the distal cranial sensory ganglia (E4-E10), the neurons of which originate from the otic and epibranchial placodes. Specific 125I beta NGF binding was also observed in various brain regions during early brain development. NGF receptor expression there followed a characteristic pattern. The neuroepithelial layer displayed very low levels of specific 125I beta NGF binding, while strong 125I beta NGF labelling was found in the mantle layer. Brainstem somatomotor nuclei, visceromotor columns, brainstem alar plate, cerebellar anlage, tectum, and basal forebrain (epithalamus, striatum) were found to be transiently labelled by 125I beta NGF in early development (E4-E12). Non-nervous tissues such as parts of the otic vesicle epithelium and skeletal muscle anlagen of the head were also labelled. These results, showing specific binding of 125I beta NGF to cranial cells of different origin (neural tube, neural crest, placode, and possibly mesoderm) strengthen the concept that NGF may have diverse functions in growth and differentiation of various tissues and cell types.

Animals↗

Expression of growth factor receptors in injured nervous tissue. I. Axotomy leads to a shift in the cellular distribution of specific beta-nerve growth factor binding in the injured and regenerating PNS.

We have studied beta-nerve growth factor (beta-NGF) receptor expression in the injured and regenerating chick PNS using [125I]-iodinated beta-NGF as a radioactive probe to map and quantitate autoradiographically the in situ distribution of specific [125I] beta-NGF binding. Two different mechanisms are involved in the reappearance of specific [125I] beta-NGF binding on the normally unlabelled adult peripheral nerves. The anterograde and retrograde axonal transport of beta-NGF binding sites leads to a rapid but transient accumulation of [125I] beta-NGF binding on both sides of crushed or transected sciatic and brachial nerves. There is a dramatic decrease in the axonal transport of beta-NGF binding sites, starting 1 day after nerve injury (1 DPO) and reaching basal levels of 10-20% of the control values at 3 to 10 DPO. Gradual but complete recovery of this axonal transport was noted in the sciatic neurites allowed to regain contact with their peripheral targets. A very different regulation pattern was observed for the local reappearance of specific [125I] beta-NGF binding on the endoneurial Schwann cells throughout the distal part of the axotomized nerve. It was first observed at 4 DPO, becoming maximal at 6 DPO. Reinnervation of the nerve after crush led to a rapid decrease of this specific [125I] beta-NGF binding, which followed a proximo-distal temporal gradient. These results show that axotomy leads to a drastic decrease in the axonal expression of [125I] beta-NGF binding, while causing its appearance on the Schwann cells of the denervated endoneurium. They suggest that these endoneurial cells may become the primary target for beta-NGF following axotomy and during regeneration.

Animals↗

Expression of growth factor receptors in injured nervous tissue. II. Induction of specific platelet-derived growth factor binding in the injured PNS is associated with a breakdown in the blood-nerve barrier and endoneurial interstitial oedema.

We have studied the expression of the platelet-derived growth factor (PDGF) receptors in the injured chick PNS using [125I]-iodinated PDGF as a radioactive probe to map autoradiographically the in situ distribution of specific [125I]PDGF binding. Crush or transection of the sciatic nerve led to a rapid and massive induction of specific [125I]PDGF binding on fibroblast-like cells of the injured endoneurium, already observed 2 h postoperatively. It is initially characterized by a symmetrical appearance both below and above the site of injury, spreading throughout the distal part of the lesioned nerve 1 to 2 days postoperatively. Comparison with distribution of specific [125I]beta-nerve growth factor (beta-NGF) binding (see preceding paper) revealed a number of important differences: unlike the specific [125I]beta-NGF binding, which rapidly disappears after reinnervation of the distal nerve, this was not observed in the case of [125I]PDGF binding. [125I]PDGF binding also correlated poorly with the extent of axonal injury. The segmental removal of the perineurium, resulting in heavy interstitial oedema without widespread axonal injury, led to a strong, local induction of [125I]PDGF binding, while causing moderate beta-NGF binding to only the few degenerating nerve fibre tubes. These results suggest the existence of different pathophysiological mechanisms that regulate the expression of PDGF and beta-NGF receptors in the lesioned and regenerating PNS.

Animals↗

The localization and distribution of high affinity beta-nerve growth factor binding sites in the central nervous system of the adult rat. A light microscopic autoradiographic study using [125I]beta-nerve growth factor.

Although beta-nerve growth factor is primarily known for its trophic role in the peripheral nervous system, recent reports have also revealed an inductive effect of beta-nerve growth factor on the cholinergic metabolism of the forebrain. To learn more about the significance and location of beta-nerve growth factor action in the central nervous system, the distribution of [125I]beta-nerve growth factor binding sites was studied by using the method of in situ receptor autoradiography and compared with the distribution of acetylcholinesterase, a sensitive enzyme marker of cholinergic neurons. The autoradiographic studies demonstrated strong, specific and saturable [125I]beta-nerve growth factor binding to several neuronal groupings in the forebrain and brainstem. beta-Nerve growth factor binding sites and strong acetylcholinesterase reactivity were jointly distributed in the forebrain on the medial septal nucleus, the diagonal band of Broca, the magnocellular basal nucleus and in the striatum. In the brainstem, beta-nerve growth factor binding sites were located on a number of neuronal groups in the reticular formation, the dorsolateral lemniscus and the cochlear nuclei. In contrast to the forebrain, less correlation was found with the distribution of acetylcholinesterase; no beta-nerve growth factor receptor expression was recorded on the cholinergic motor nuclei of the brainstem, while specific [125I]beta-nerve growth factor labeling could be located on the non-cholinergic cochlear nuclei. The present autoradiographic studies reveal a variety of tentatively beta-nerve growth factor receptor-positive neurons in the central nervous system. While strong correlation between the cholinergic metabolism and the presence of specific beta-nerve growth factor binding is demonstrated in the forebrain, this observation could not be extended to the brainstem, indicating the chemical diversity of central beta-nerve growth factor receptor-positive neurons.

Acetylcholinesterase↗

The spatial and temporal pattern of beta NGF receptor expression in the developing chick embryo.

To gain insight into the developmental program of nerve growth factor (NGF) receptor expression, the binding of [125I] beta NGF to frozen chick sections was investigated autorradiographically between embryonic day 3 (E3) and post-hatching day 3. Strong NGF receptor expression was observed as early as E4, throughout embryonic development and in the post-hatching period at the classical NGF target sites: the paravertebral sensory and sympathetic ganglia, the paraaortal sympathetic ganglia as well as the cranial sensory ganglia with neurons of neural crest origin and their respective nerves. Only weak [125I] beta NGF binding was observed during a restricted time span in the parasympathetic ciliary ganglion. Clear differences were observed in the intensity and in the developmental time course of [125I] beta NGF binding to the dorsomedial and ventrolateral aspects of the dorsal root ganglia. NGF receptors were also found to be expressed on central axons of the dorsal root entry zone and the dorsal tract in the spinal cord. A transient expression of specific NGF binding sites of the same high affinity as measured at the classical NGF targets, was detected in the lateral motor column and in muscle at the time of motoneuron synapse formation and elimination.

Age Factors↗