PubMed Health⌕ Search

Biomedical subjects

J M Rigo

Publications and source records attributed to J M Rigo.

12 recordsLinked to original sources
PubMed1992

In vitro and in vivo modulation of 5-hydroxytryptamine-, thyrotropin-releasing hormone- and calcitonin-gene related peptide-like immunoreactivities in adult rat sensory neurons.

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect.

Animals↗
PubMed1992

Peripheral and central target-derived trophic factor(s) effects on auditory neurons.

In the developing inner ear, a naturally occurring programmed cell death of cochleovestibular ganglion (CVG) neurons as well as peripheral and central target-derived trophic effects on survival of embryonic CVG neurons are known. To further analyze these target derived trophic interactions, spiral ganglion explants obtained from 5 day postpartum (P5) rat pups were cultured with an intact organ of Corti and in the absence of Corti's organ. Both neuronal survival and neurite extension were influenced by the presence of this peripheral target tissue. Local destruction of Corti's organ caused both neuritic retraction and neuronal cell death to occur in a corresponding portion of the spiral ganglion. This peripheral target-derived neurotrophic effect may be mediated by a diffusible factor(s) since organ of Corti conditioned medium also had a neurotrophic effect on the survival of auditory neurons in cell cultures of dissociated spiral ganglia from P5 rat pups. A component of central target tissue, i.e. astrocytes, was also shown to release a diffusible factor(s) that supported the survival of dissociated P5 rat spiral ganglion neurons. The neurotrophic effects on the in vitro survival of spiral ganglion neurons by both of these conditioned medium factors were concentration dependent.

Animals↗
PubMed1991

Kainate and NMDA toxicity for cultured developing and adult rat spiral ganglion neurons: further evidence for a glutamatergic excitatory neurotransmission at the inner hair cell synapse.

In the inner ear, the excitatory amino acid glutamate is a proposed neurotransmitter acting at the synapse between hair cells and afferent auditory neurons. Using cultures of 5-day-old rat auditory neurons, we show that the afferent auditory neuronal population can be divided, on the basis of its sensitivity to the neuronotoxic effect of glutamate and its analogs, in at least 3 subpopulations, one responding to N-methyl-D-aspartate (NMDA), one responding to kainate and a third minor one unresponsive to NMDA, kainic acid and glutamate. No toxic effect of quisqualate is observed. The use of specific antagonists (kynurenate and 2-amino-5-phosphonovalerate (DAP-5) demonstrates the specificity of the receptors to the excitatory amino acids on the afferent auditory neurons. Afferent auditory neurons from adult rats can also be cultured and in these preparations only the large neurons are sensitive to glutamate, kainate and NMDA while the small neurons are not responsive, suggesting that a glutamatergic neurotransmission occurs only at this synapse between the inner hair cells and the large radial afferent auditory neurons. We also show that, in vitro, the organ of Corti releases, in response to an increased potassium concentration and in the presence of calcium, a toxic activity for the afferent auditory neurons that is antagonized by kynurenate and DAP-5. Pathophysiological implications are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1991

Modulation of proteolytic activity during neuritogenesis in the PC12 nerve cell: differential control of plasminogen activator and plasminogen activator inhibitor activities by nerve growth factor and dibutyryl-cyclic AMP.

Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 nerve cells were used to study the modulation of proteolytic activity during neuronal differentiation. PC12 cells were found to contain and release a 70-75-kDa tissue-type plasminogen activator (tPA) and a much less abundant 48-kDa urokinase-type plasminogen activator. A plasminogen activator inhibitor (PAI) activity with molecular sizes of 54 and 58 kDa was also detected in PC12 cell conditioned medium and formed high-molecular-mass complexes with released tPA. Release of PAI activity was dependent on treatment with nerve growth factor (NGF), whereas tPA synthesis and release were under control of a cyclic AMP-dependent mechanism and increased on treatment with dibutyryl-cyclic AMP [(But)2cAMP] or cholera toxin. Simultaneous treatment with NGF and (But)2cAMP resulted in increases of both tPA and PAI release and enhancement of tPA-PAI complex formation. The resulting plasminogen activator activity in conditioned medium was high in (But)2cAMP-treated cultures with short neuritic outgrowth but remained low in NGF- or NGF plus (But)2cAMP-treated cultures, where neurite extension was, respectively, large and very large. These results suggest that excess proteolytic activity may be detrimental to neuritic outgrowth and that not only PAI release but also tPA-PAI complex formation is associated with production of large and stable neuritic outgrowth. This can be understood as an involvement of PAI in the protection against neurite-destabilizing proteolytic activity.

Adrenal Gland Neoplasms↗
PubMed1990

Potassium-induced release of an endogenous toxic activity for outer hair cells and auditory neurons in the cochlea: a new pathophysiological mechanism in Menière's disease?

In Menière's disease, the increase of extracellular potassium concentration in the perilymph is thought to play a key role in determining the progressive loss of cochlear hair cells. In this paper, we describe a serum-free culture preparation of hair cells from 5 day-old rat and report the release by the cochlea, in response to an increase of extracellular potassium concentration, of a cytotoxic activity active on hair cells and auditory neurons. The toxic activity is associated with low molecular weight (less than 10,000 Dalton) molecule(s) as revealed by ultrafiltration. Morphological studies performed on the organ of Corti incubated during 24 h in the presence of the cochlea-derived toxic activity (CTA), show that this factor is toxic for hair cells and not for supporting or surrounding cells. The release of CTA occurs both in the spiral ganglion and in the organ of Corti. We suggest that this cochlea-derived toxic activity may play an important role in the pathophysiology of the hearing loss that occurs during the progression of Menière's disease.

Animals↗
PubMed1990

Neuronotrophic effect of developing otic vesicle on cochleo-vestibular neurons: evidence for nerve growth factor involvement.

In the developing inner ear, the existence of a neuronal death and of a peripheral target-derived trophic effect on cochleovestibular neurons has been documented. Using cultures of rat cochleovestibular neurons, we show that the E12 otic vesicle releases a factor promoting the survival and the neuritogenesis of these neurons, and that this effect is mimicked by NGF. The effect of the optic vesicle conditioned medium (OVCM) on cochleovestibular neurons is suppressed by anti-NGF antibodies. OVCM is neuronotrophic for NGF-sensitive sympathetic neurons, an effect that is also suppressed by anti-NGF antibodies, further demonstrating the presence of biologically active nerve growth factor.

Adrenergic Fibers↗
PubMed1990

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine).

Using in vitro techniques, we looked for a possible downregulation of rat astroglia proliferation by neuronal cells. We demonstrate that medium conditioned by 7-day-old rat cerebellar granule neurons or by 16-day-old rat embryo hippocampal neurons strongly inhibits the proliferation of cultured astroglial cells. Two neuronal cell lines, the PC12 rat pheocromocytoma and the neuro 2A (N2A) murine neuroblastoma also release such an activity. This release in N2A-conditioned medium (CM) occurs when the cells are at high density and show a low proliferation rate. This activity is present in media conditioned by neuronal cells, but not in media conditioned by normal astrocytes, by two glioma cell lines, or by one fibroblastic cell line. This proliferation inhibitor addresses normal astrocytes: the proliferation of two glioma cell lines, of a fibroblastic cell line, and of the two neuronal cell lines (PC12, N2A) is not inhibited by N2A CM. Moreover, this activity is directed against type 1 astrocytes, but not against type 2. Using three different assays, we demonstrate that DNA synthesis by astroglial cells is inhibited. N2A CM has no cytotoxic effect on astrocytes and does not modify their overall protein synthesis. Using affinity and gel filtration chromatography, we show that this activity is associated with a protein whose molecular weight ranges between 15 and 20 kDa. The possible relationship between this N2A cell-derived astroglia proliferation inhibitor and other types of potential glial proliferation inhibitors has been investigated. A brain glycoprotein immunologically related to epidermal growth factor receptor (EGFR) was reported to inhibit astroglial cell proliferation in vitro. Using polyclonal and monoclonal antibodies against EGFR, we were unable to immunoprecipitate the astrocyte proliferation inhibitor in N2A CM or to demonstrate by immunoblotting the presence of an EGFR-like immunoreactivity in the N2A CM or in the active chromatographic fractions of N2A CM. Transforming growth factor beta (TGF beta) is a well-known modulator of the proliferation of various cell types and was shown to be present in N2A CM. Using a polyclonal anti-TGF beta antibody that recognizes TGF beta on Western blots of N2A CM, we were unable to immunoprecipitate the astrocyte proliferation inhibitor of N2A CM. It seems thus far that the neuronal astroglia proliferation inhibitor is a new protein for which we propose the name astrostatine.

Animals↗
PubMed1989

Cultured astroglia release a neuronotoxic activity that is not related to the excitotoxins.

Neuronal death after brain injury is thought to be in part the result of the activity of the excitotoxins, a family of excitatory amino acids which are released by neurones. We have also described an astroglial cell-derived neuronotoxic activity of low molecular weight whose release can be induced by depolarizing events such as an increase in extracellular potassium concentration. We study here the relationship between this astroglia-derived neuronotoxic activity present in astroglia-conditioned medium (ACM) and the excitotoxins. Using a colorimetric assay of neuronal survival, we show that the ACM neuronotoxic activity, is able to induce the death of all types of neurones tested, including those which are insensitive to excitotoxins. Furthermore, the ACM neuronotoxic activity does not require for its action the extracellular ionic composition which is needed for the activity of excitotoxins. Finally, the ACM neuronotoxic activity is not blocked by competitive or non-competitive antagonists of the various classes of excitotoxin receptors. Those data demonstrate that the astroglia-derived neuronotoxic activity is not related to the excitotoxins. Still, because astrocytes can also be depolarized by members of the excitotoxin family, the possibility exists that the release of astroglia-derived neuronotoxic activity would follow the rise in extracellular excitatory amino acid concentration during nervous system injury.

Amino Acids↗
PubMed1989

In vitro kinetics of a newborn rat astroglia-derived neuronotoxic activity.

A low-molecular weight astrocyte-derived neuronotoxic activity (ANTA) was detected, using a colorimetric bioassay of cell survival, by its effect on cultured granule cells. This neuronotoxic activity was found to be released rapidly from newborn rat astrocytes in culture upon incubation in 50 mM K+-containing growth medium. The release by astrocytes could be induced repetitively by successive incubations in high-K+ medium alternating with incubations in normal medium. Astrocytes were also found to inactivate rapidly isobutanol-extracted ANTA in normal K+-containing growth medium. Kinetic studies showed that ANTA induces a slow (greater than 12 h) degeneration of cultured granule cells. ANTA is shown here to be an intermediate of normal astrocyte metabolism and to display appropriate kinetic characteristics compatible with its proposed role in inducing part of the delayed neuronal loss that occurs after a brain injury (secondary neuronal death).

Animals↗
PubMed1989

[Neuronotrophic interactions in the developing inner ear].

In the developing inner ear, the existence of a neuronal death and of a peripheral target-derived trophic effect on the embryonic cochleovestibular neurons is described. We investigate the molecular vector(s) of such neuronotrophic influences on the cochleovestibular neurons, particularly the nerve growth factor (NGF) which is a good candidate since receptors for this trophic factor are described in the embryonic inner ear. In 12 day-old rat embryos, we demonstrate the release of an NGF-like activity by the otic vesicle and the effect of this trophic factor on the survival and the neuritogenesis of the cochleovestibular neurons. We suggest an important role for NGF in the neuronal stabilisation of the cochleovestibular ganglion and the invasion of the otic vesicle by the neurites. The study of the neuronotrophic interactions in the inner ear is then applied on more mature auditory neurons. In the 5 day-old rat cochlea, we also show the release by the central and the peripheral targets of a trophic activity allowing the survival of the afferent auditory neurons. These neuronotrophic factors may play an important role in the secondary degeneration of the auditory neurons following an injury of the Corti's organ or of the central target. The effect of NGF is also investigated on these neurons and we demonstrate that NGF has a neuritogenic but not a survival promoting effect on the 5 day-old rat afferent auditory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗