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ABSTRACT: The hyaluronan receptor for hyaluronic acid-mediated motility (RHAMM) plays a role in cell migration and motility in many systems. Recent observations on the involvement of RHAMM in neurite motility in vitro suggest that it might also be important in axon outgrowth in situ. This was addressed directly by investigating both RHAMM expression in the rat CNS and the ability of anti-RHAMM reagents to interfere with tissue growth and axon outgrowth in intraocular brainstem transplants. By western blotting, anti-RHAMM antibody detected a RHAMM isoform of 75,000 mol. wt in both whole brain homogenate and synaptosome preparations, and a 65,000 mol. wt isoform in synaptosomes. Immunofluorescence of adult brain sections revealed RHAMM-like immunoreactivity in varicose fibers that were also positive for the noradrenergic marker dopamine-beta-hydroxylase. Not all noradrenergic fibers contained RHAMM, nor was RHAMM detected in other monoaminergic fiber types. Lesions of noradrenergic fiber systems with beta-halobenzylamine-N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) eliminated RHAMM-positive fibers, but noradrenergic axons that sprouted extensively after this treatment were strongly RHAMM-positive. To assess RHAMM's role in fiber outgrowth, fetal brainstem tissue containing noradrenergic neurons was grafted into the anterior chamber of the eye. Treatment of grafts with anti-RHAMM antibody caused significant inhibition of tissue growth and axon outgrowth, as did a peptide corresponding to a hyaluronan binding domain of RHAMM. These agents had no such effects on transplants containing serotonergic and dopaminergic neurons. These results suggest that RHAMM, an extracellular matrix receptor previously shown to contribute to migratory and contact behavior of cells, may also be important in the growth and/or regenerative capacity of central noradrenergic fibers originating from the locus coeruleus.
Neuroscience 10/1998; 86(1):241-55. · 3.38 Impact Factor
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ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-beta superfamily of growth factors with marked neurotrophic activity on midbrain dopaminergic neurons. To investigate whether this trophic activity is shared by central cholinergic neurons, we investigated the effects of GDNF treatment during development of the medial septal area in rats. Adult Fischer 344 rats received intraocular transplants of fetal septal forebrain tissue (embryonic Day 17) which was preincubated for 20 min with either GDNF or vehicle. The two treatment groups subsequently received weekly intraocular injections of either GDNF (0.5 microgram in 5 microliters/injection) or vehicle for 6 weeks following transplantation. Transplants treated with GDNF grew twice as large as control grafts treated with vehicle. Immunohistochemical evaluations of the transplants revealed that there was no difference between the two groups in terms of acetylcholinesterase or low affinity neurotrophin receptor (p75) staining. In contrast, a significant increment in the number of GABA-ergic neurons was observed in transplants that received GDNF, as compared to vehicle-treated grafts. The overall number of neurons within the transplanted tissue was also elevated in the experimental group. There was no difference between the two groups in the distribution or density of astrocytes in the grafted tissue, as evidenced by immunohistochemistry with antibodies directed against glial fibrillary acidic protein. These results indicate that basal forebrain GABA-ergic neurons may be dependent on GDNF for their survival and/or for GABA synthesis, but that the cholinergic neurons in this area appear to be unaffected by GDNF administration during development.
Experimental Neurology 11/1996; 141(2):181-9. · 4.70 Impact Factor
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ABSTRACT: We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the non-glomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons.
Cell and Tissue Research 11/1995; 282(1):49-57. · 3.11 Impact Factor
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ABSTRACT: The present study was undertaken to evaluate innervation and possible growth promotion by posterior hypothalamic tissue on different areas that are, or are not, interactive with this brain region during development. Posterolateral hypothalamus was dissected from embryonic day 17 rat fetuses, and inserted into the anterior chamber of the eye of adult rat hosts. Two weeks postgrafting, a second transplant consisting of either fetal hippocampal, cerebellar, or lung tissue was placed adjacent to the first graft. Growth of the intraocular double transplants was monitored weekly by measurements through the cornea. Fetal hippocampal tissue grew significantly larger when placed together with a hypothalamic graft, as compared to single hippocampal transplants. Cerebellar or lung tissue growth was not stimulated by a hypothalamic cograft. Pyramidal neuron cell counts demonstrated a significantly higher final number of these neurons in growth-stimulated hippocampal grafts, as compared to non-stimulated single hippocampal grafts. Immunohistochemistry with antibodies directed against histamine or histidine decarboxylase revealed that hippocampal transplants received the most dense histaminergic innervation. Cerebellar transplants contained occasional histaminergic neurites, and lung tissue never exhibited any histaminergic innervation from the adjacent hypothalamic graft. Taken together, these results demonstrate a growth-promoting effect of posterior hypothalamic tissue on developing hippocampal tissue, as well as target specificity of histaminergic innervation patterns.
Hippocampus 02/1995; 5(6):584-94. · 5.18 Impact Factor
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ABSTRACT: Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-β superfamily of growth factors with marked neurotrophic activity on midbrain dopaminergic neurons. To investigate whether this trophic activity is shared by central cholinergic neurons, we investigated the effects of GDNF treatment during development of the medial septal area in rats. Adult Fischer 344 rats received intraocular transplants of fetal septal forebrain tissue (embryonic Day 17) which was preincubated for 20 min with either GDNF or vehicle. The two treatment groups subsequently received weekly intraocular injections of either GDNF (0.5 μg in 5 μl/injection) or vehicle for 6 weeks following transplantation. Transplants treated with GDNF grew twice as large as control grafts treated with vehicle. Immunohistochemical evaluations of the transplants revealed that there was no difference between the two groups in terms of acetylcholinesterase or low affinity neurotrophin receptor (p75) staining. In contrast, a significant increment in the number of GABA-ergic neurons was observed in transplants that received GDNF, as compared to vehicle-treated grafts. The overall number of neurons within the transplanted tissue was also elevated in the experimental group. There was no difference between the two groups in the distribution or density of astrocytes in the grafted tissue, as evidenced by immunohistochemistry with antibodies directed against glial fibrillary acidic protein. These results indicate that basal forebrain GABA-ergic neurons may be dependent on GDNF for their survival and/or for GABA synthesis, but that the cholinergic neurons in this area appear to be unaffected by GDNF administration during development.
Experimental Neurology.
