PubMed Health⌕ Search

Biomedical subjects

G Despres

Publications and source records attributed to G Despres.

12 recordsLinked to original sources

Distribution of glial fibrillary acidic protein (GFAP) in the cochlear nucleus of adult and aged rats.

The age-related change in glial fibrillary acidic protein (GFAP) immunoreactivity was analyzed in young (3 months) and old (24 months) adult rat cochlear nuclei (CN). Quantitative analyses show a significant increase with age, in the number of GFAP positive astrocytes and processes in the old adult when compared with the young adult rat. There was also a differential distribution of GFAP immunoreactivity in the young adult CN where it predominates in the granular cell region, whereas in old rats, the GFAP immunoreactivity distribution was homogeneous in all parts of the nucleus. There was no change in the total number of neurons between these two stages in any part of the nucleus except for the antero-ventral CN, where a decrease in neuronal number was observed in the aged rats. The increase in GFAP immunoreactivity was related to an increase of both GFAP positive astrocyte number and processes. The increase of GFAP positive astrocytes may be due either to an alteration of auditory nerve fibers, changing the trophic interactions with post-synaptic cells, or to intrinsic alterations of CN neurons and local circuits reflecting aging of the CN.

Aging↗

Histochemical and scanning electron microscopic studies of supernumerary hair cells in embryonic rat cochlea in vitro.

In the embryonic organ of Corti supernumerary hair cells were observed when developed in organotypic cultures. Hair cells ranging in up to two rows of inner hair cells (IHCs) and up to nine rows of outer hair cells (OHCs), were observed by phalloidin histochemistry. The total number of hair cells may double in some explanted cochleae compared to control ones. Cuticular plates of hair cells displayed an actin-free zone corresponding to the kinocilium location, differently located and indicating different degrees of differentiation and maturation. Moreover, some hair cells had a small apical surface area and a centrally located kinocilium, revealing immaturity. Under scanning electron microscopy, stereocilia appeared to differentiate normally, as compared to the in vivo development. The staircase pattern of the stereociliary bundles was reached on most of the hair cells with a 'V' shape on the OHCs and hemispherical one on the IHCs. Hair cell polarity was not homogeneous along the length of the tissue. Organs of Corti explanted at birth developed a weaker number of supernumerary hair cells showing a decrease of supernumerary hair cells with the developmental stage of the explant. These results provide evidence for supernumerary hair cells in the mammalian cochlea in culture, without loss or injury to preexisting hair cells.

Animals↗

Distribution and metabolism patterns of plasma 7S- and beta-NGF in the adult male rat.

There is a great deal of controversy on the existence of NGF in body fluids and tissues. To date it remains unknown whether this peptide accumulates preferentially at significant levels in different organs. Thus we undertook the evaluation of kinetic parameters of the disappearance of blood of 125I-7S-NGF and 125I-beta-NGF after intravenous injection in male adult rats. Our results indicate that the plasma half-life of 125I-7S-NGF is approximately twice as long as for 125I-beta-NGF (respectively 61.7 +/- 11.7 min and 36.3 +/- 2.2 min) while the distribution volume is not significantly different between both peptides. Furthermore, the uptake of radioactive NGF by different tissues seems very low as shown by 125I-7S-NGF and 125I-beta-NGF content of the sampled organs compared to the plasma concentration at the same time. These results indicate that the tissue uptake of circulating 7S and beta-NGF is very low in the adult rat. Thus in these animals NGF did not cross the blood-brain barrier and did not accumulate in peripheral organs which are known to contain subsequent amounts of this peptide. This lack of deposition might be due to a binding with plasma proteins (probably alpha 2-macroglobulin).

Animals↗

Hair cell overproduction in the developing mammalian cochlea in culture.

Hair cells transduce acoustics into electrical signals that are conveyed to the brain by auditory nerve fibres. Hair cells loss in mammals due to ageing, ototoxic drugs or noise, leads to irreversible hearing impairment. One objective would be to replace lost cells by regeneration or production of new hair cells. We report an overproduction of hair cells in the developing cochlea of the rat in culture without adding drugs, without previous injury or special manipulations of the explants. The overproduction of hair cells does not depend on the culture medium or on the innervation of the organ of Corti. Younger foetal explants show higher potency for the production of supplementary hair cells than older ones. This is the first report of the generation of extra hair cells in mammals without previous hair cell loss or treatment with drugs.

Aging↗

Cochlear innervation in the developing rat: an immunocytochemical study of neurofilament and spectrin proteins.

We have studied the innervation of the developing cochlea by immunocytochemical staining of the cytoskeletal proteins, neurofilament (NF), and spectrin (brain spectrin and erythrocyte spectrin). NF immunoreactivity was seen in spiral ganglion cell bodies and their processes and in fibers of the intraganglionic spiral bundle (IGSB) on gestational day 16. NF immunoreactivity with monoclonal antibodies to NF160 and NF68 was present beneath both inner hair cells (the IHC) and outer hair cells (OHCs) on gestational day 20. NF200 immunostaining was located only in the IGSB and in fibers reaching the IHC. The first NF200 immunoreactivity beneath the OHCs was seen in the basal turn at birth. NF labelling began to decrease on postnatal day 9 and its intensity became more like that of the adult. Brain spectrin immunostaining was first seen in the IGSB of the basal turn on gestational day 18. It reached the fibers between the spiral ganglion and the IHC on gestational day 20. Brain spectrin immunoreactivity was first seen beneath the OHCs in the basal turn at birth. It reached all the OHCs of the cochlea by postnatal day 4, and began to decrease 9 days after birth. Erythrocyte spectrin immunostaining was first observed during the second postnatal week, when it labelled spiral ganglion cells. The distribution of NF200 and brain spectrin immunoreactivity suggested that efferent innervation of OHCs is present at birth in the rat, and confirms previous studies showing the early efferent innervation of the OHCs of the mouse and the rat at birth, and the time lag between the appearance of the two spectrin isoforms during development.

Aging↗

Immunocytochemical localization of neurofilament protein subunits in the spiral ganglion of the adult rat.

Spiral ganglion neurons from adult rats were treated with several monoclonal antibodies that react with neurofilaments (NFs) and NF subunits. An antibody against NFs used with immunocytochemical techniques showed a strong reaction with most neuron processes in the spiral ganglion, whereas only a few neurons presented a reaction. Using monoclonal antibodies against the 3 subunits, we obtained the same results with a small percentage of neurons labelled. From quantitative observations, reacting neurons showed the same percentage as and a smaller size than T II neurons observed with a more conventional method. This shows that reacting neurons are indeed T II neurons and that they can easily be differentiated by an accumulation of NFs in their perikaryon by well characterized commercially available antibodies.

Animals↗

Immunohistochemical localisation of nerve growth factor-like protein in the organ of Corti of the developing rat.

The presence of nerve growth factor (NGF)-like protein was investigated in the cochlea of the developing rat between birth and postnatal day 30, by the indirect immunofluorescence technique. Nerve growth factor-like protein could be detected from birth up to day 8. The immunostaining was localised within the hair mainly above their nuclei. No NGF-like immunoreactivity was observed in spiral ganglion cells. The data suggest that NGF acts as a neurotrophic factor, especially for efferent endings in the developing cochlea.

Aging↗

Factors affecting the onset of inner ear function.

The developing inner ear receptors have a very significant influence on the onset of stato-acoustic function and on its evolution. The factors which prevent the stato-acoustic system from functioning are called 'the limiting factors'. At present, it is possible to postulate that these factors are restricted to the inner ear cells and related structures. At least four places are particularly relevant for the onset of function: (1) connections of the apical part of hair cell with the tectorial membrane; (2) the internal structure of hair cell; (3) connections between the base of the hair cell and nerve fibers; (4) the ganglion cell with its processes. Special emphasis is devoted to the apical part of the inner hair cell and its connections to the tectorial membrane which are considered as very important for the onset of the cochlear function. For the labyrinth, it is technically difficult to determine precisely the onset of function because of its early prenatal onset. Nevertheless, it is postulated that the limiting factors for the onset of function are also related to certain components of hair cells.

Animals↗

Transfer of maternal testosterone to the guinea pig fetus during the last third of pregnancy.

Testosterone (T) transfer from mother to fetuses was explored in anesthetized guinea pigs on Days 48 and 67 of pregnancy using a constant intravenous infusion of tritium-labeled T ([3H]T). Labeled dihydrotestosterone ([3H] DHT), androstenedione ([3H] delta 4) and [3H] T were estimated after celite chromatography in maternal plasma, umbilical venous plasma, fetal arteriovenous plasma and fetal tissue homogenates including liver, genital tract with gonads, hypothalamic area, hypophysis and remaining brain. Total radioactivity was measured by counting a part of the homogenates. Results indicate that very low concentrations of [3H] T and [3H] delta 4 were found in umbilical and fetal plasma, whereas [3H] DHT levels were relatively high. A minute part of maternal T was transferred to male and female fetuses: 0.7 to 1.9 pg/ml, and that represented 0.4 to 5.6% of fetal T. The difference observed between umbilical and fetal [3H] T showed that 80% of the fetal T coming from the mother was metabolized by the fetuses. This result is discussed in relationship to the high radioactive concentrations present in fetal liver. Concentrations of total radioactivity were high in fetal tissues, and the three nervous tissues exhibited a significant difference in their capacity to fix radioactivity. There was a complete absence of the three labeled androgens in the hypophysis. However, [3H] DHT was present in all other tissues, and gonads + genital tract in the male fetus exhibited [3H] DHT concentrations significantly higher than those detected in the female fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alterations in the androgen metabolism of the female guinea-pig during pregnancy.

The peripheral conversion of testosterone (T) into androstenedione (delta 4) and dihydrotestosterone (DHT) were studied in pregnant (days 32, 48 and 67 post coitum) and non-pregnant anesthetized guinea-pigs by constant intravenous infusion of tritium labeled T. Endogenous levels were measured by radioimmunoassay, and the three labeled androgens (T*, DHT* and delta 4*) counted after celite chromatography. The endogenous T, DHT and delta 4 plasma concentrations were respectively 5, 7 and 20 times higher in pregnant females than they were in cyclic ones. In the non-pregnant guinea-pig, no part of the delta 4 or DHT pools was derived from the peripheral conversion of testosterone. On days 32, 48 and 67 of gestation the fractions of the delta 4 pool originating from T were 9.1, 13.1 and 15.1%, and the fractions of DHT pool coming from T were 5.1, 22.1 and 21.3% respectively.

Androgens↗

Changes in the metabolic clearance rate and plasma production rate of testosterone in the pregnant guinea-pig.

The metabolic clearance rate of testosterone (MCRT) in the pregnant and non-pregnant guinea-pig was established by a constant infusion method to steady state levels of 3H testosterone (T). Simultaneously, the concentration of endogenous T was determined by radioimmunoassay and the production rate of T (PRT) was calculated from the product of MCRT and endogenous T concentration. Results indicate important alterations in the three parameters between non-pregnant (MCRT = 64.0 +/- 2.6 1/24 hr; T concentration = 51 +/- 8 pg/ml; PRT = 3.24 +/- 0.13 micrograms/24 h) and the pregnant guinea-pig. In these animals mean values from day 43 were about 33 1/24 h for MCRT, 378 pg/ml for T concentrations and 12.5 micrograms/24 h for PRT. The significance of these results is discussed in relation to the specific binding of testosterone with the progesterone binding globulin during pregnancy in this species.

Animals↗