Christiane Legrand

Effects of Hypothyroidism on the Structural Development of the Organ of Corti in the Rat

The structural development of the organ of Corti was studied in 30 rat pups rendered hypothyroid by daily administration of propylthiouracil during the first 35 days after birth. Cochlear changes were observed by light microscopy and electronmicroscopy. Hypothyroid rat pups were found to have severe abnormalities in the organ of Corti. There was an abnormally prolonged persistence of Köllikers organ and striking distortion of the tectorial membrane. The sensory epithelium exhibited marked signs of immaturity: the tunnel of Corti has not opened yet in animals 35 days old, sensory and supporting cells presented immature characteristics with abnormal persistence of the kinocilium. It is suggested that hypothyroidism results in an overall retardation of the maturation of cochlear structures and ultrastructural changes that appear to be significant enough to account for the hearing loss.

Maturational and degenerative processes in the organ of Corti after neonatal hypothyroidism

In order to study the long-term effects of neonatal hypothyroidism on the organ of Corti, rats were given propylthiouracil (PTU) during the first 30 days after birth. Cochlear changes occurring after the cessation of antithyroid treatment were studied by both physiological (brainstem auditory evoked responses: BAERs, electrocochleography) and morphological techniques (transmission and scanning electron microscopy). The first appearance of BAERs was noted between days 37 and 45. Maturation of auditory potentials was achieved within 10-15 days but was incomplete since the animals definitely demonstrated elevated thresholds around 60-70 dB SPL. Morphological results indicated that some structures, like the inner sulcus epithelium, were able to restart maturational processes that had been interrupted during the period of hypothyroidism. However, these maturational changes were considerably limited and rapidLy accompanied by severe degenerative changes involving almost all cochlear structures. Degenerative changes included the deposition of an amorphous substance within the organ of Corti, severe alterations in pillar cells (absence of formation of the tunnel of Corti, distortion of microtubules), severe outer hair cell losses with abnormalities in their innervation (absence of development of efferents and loss of afferent dendrites).

Corrective effects of thyroxine on cochlear abnormalities induced by congenital hypothyroidism in the rat. II. Electrophysiological study

In order to study the corrective effects of thyroxine (T4) on functional abnormalities induced by congenital hypothyroidism, small doses of T4 were injected to propylthiouracil-treated (PTU-treated) rat pups for 2 consecutive days on selected periods of development (days 3 and 4, 6 and 7, 9 and 10, 12 and 13, 18 and 19). Some animals also received thyroid replacement therapy from days 12 to 17. The animals were tested electrophysiologically on day 30, by recording the compound action potential and the cochlear microphonic from the round window after click and tone burst stimulation. PTU-treated animals given T4 for 2 consecutive days demonstrated both AP and CM threshold shifts. On the contrary, PTU-treated animals given T4 from days 12 to 17 demonstrated a normal CM output of the cochlea, but still showed elevated AP thresholds. These results are discussed with previous data concerning the corrective effects of T4 on cochlear structures in PTU-treated rats previously described.

Cochlear synaptogenesis in the hypothyroid rat.

The effects of congenital hypothyroidism on cochlear synaptogenesis were studied using transmission electron microscopy in 30 propylthiouracil-treated rat pups 1-35 days of age. No difference with controls was observed at the level of the inner hair cells which are known to mature essentially during the prenatal period. On the contrary, hypothyroidism resulted in numerous abnormalities in synaptogenesis at the level of the outer hair cells: abnormal persistence of numerous afferent dendrites and presynaptic specializations, incomplete development of efferent terminals and absence of formation of postsynaptic cisterns. It can be concluded that hypothyroidism results in severe retardation in the postnatal development of the innervation of outer hair cells.

Conducting interpenetrating polymer network sized to fabricate microactuators

Interpenetrating polymer networks can become successful actuators in the field of microsystems providing they are compatible with microtechnologies. In this letter, we report on a material synthesized from poly(3,4-ethylenedioxythiophene) and polytetrahydrofuran/poly(ethylene oxide) and microsized by decreasing its thickness to 12 μm and patterning the lateral side using plasma etching at high etch rates and with vertical sidewalls. A chemical process and a “self degradation” are proposed to explain such etching rates. Preliminary actuation results show that microbeams can move with very large displacements. These microsized actuators are potential candidates in numerous applications, including microswitches, microvalves, microoptical instrumentation, and microrobotics.

Amplified piezoelectric transduction of nanoscale motion in gallium nitride electromechanical resonators

A fully integrated electromechanical resonator is described that is based on high mobility piezoelectric semiconductors for actuation and detection of nanoscale motion. We employ the two-dimensional electron gas present at an AlGaN/GaN interface and the piezoelectric properties of this heterostructure to demonstrate a resonant high-electron-mobility transistor enabling the detection of strain variation. In this device, we take advantage of the polarization field divergence originated by mechanical flexural modes for generating piezoelectric doping. This enables a modulation of carrier density which results in a large current flow and thus constitutes a motion detector with intrinsic amplification.

Diamond-like carbon films as electron-injection layer in organic light emitting diodes

In this letter a thin film of diamond-like carbon (DLC) deposited by pulse laser deposition (PLD) is used as an electron injection layer in organic light emitting diodes. The heterojunction structures of these devices consist of: indium tin oxide (ITO)/conducting polymer/DLC/nickel, or ITO/DLC/P3OT/Pt. Poly(3-octylthiophene) conjugated polymer (P3OT) is used as the emission layer. In all the realized diodes, the current is two orders of magnitude larger than in the conventional ITO/P3OT/aluminum structure, and the driving voltage is drastically reduced. However, the light emission is observed only in the ITO/DLC/P3OT/Pt structure. These results can be interpreted in terms of a highly efficient electron injection from the DLC into the conducting polymer and a DLC/P3OT interface.

Immunocytochemical localisation of Gelsolin in Oligodendroglia of the developing rabbit central nervous system

Antibodies raised against gelsolin of rabbit lung macrophages were used in an immunocytochemical study during development of the rabbit central nervous system. With the exception of a transient staining of the cerebellar Purkinje cells during the first postnatal week, gelsolin was found a new marker for oligodendrocytes, especially in developing animals. In the macrophages, gelsolin is involved in the control of locomotion, secretion and endocytosis. In the oligodendrocytes, which produce the myelin sheaths in the central nervous system, gelsolin could therefore be involved in the control of the complex motile events leading to myelin wrapping.

Microtubules in the cochlea of the hypothyroid developing rat

In order to study the effects of hypothyroidism on the development of microtubules in the cochlea, rat pups were rendered hypothyroid by daily administration of propylthiouracil. Microtubules were studied by immunofluorescence and electron microscopy. The absence of immunostaining of pillar cells with antimicrotubule or antitubulin antibodies was correlated with a retarded morphological development of microtubules within these same structures. The above alterations induced an abnormal development of pillar cells, non-appearance of the tunnel of Corti, and stunted epithelial growth. In contrast, a distinct immunoreaction was observed under the outer hair cells. This was attributed to abnormal persistence of afferent dendrites containing microtubules. The results suggest that, while the effect of thyroid hormone on microtubules in afferent cochlear dendrites could not be demonstrated, thyroid hormone is necessary for the normal development of microtubules in epithelial structures.

Cholecalcin (28-kDa CaBP) in the rat cochlea. Development in normal and hypothyroid animals. An immunocytochemical study

The distribution of cholecalcin (28-kDa calcium-binding protein) in the cochlea of developing rats was followed by immunocytochemistry. In normal animals, the protein first appeared in utero in the cells of Köllikers organ, a structure involved in the secretion of the tectorial membrane. The inner hair cells, followed by the outer hair cells, then became immunoreactive from the base of the cochlea to the apex. Their cuticular plate, the anchoring structure for stereocilia, was particularly labeled. The cells of Köllikers organ lost their immunoreactivity after the first postnatal week, the time when they lose their secretory activity. During the same period, when the tunnel of Corti and the space of Nuel open, labeling appeared in the supporting cells. The neurons of the spiral ganglion were stained from the second postnatal week and the fibers of the cochlear nerve after the end of the first month. No difference was induced by thyroid deficiency until the second postnatal week. Thereafter, Köllikers organ did not transform and its cholecalcin immunoreactivity persisted, together with the secretory activity. As a result, the tectorial membrane was greatly distorted and the mechanical properties of the organ of Corti were dramatically impaired. The supporting cells were labeled although the tunnel of Corti and the space of Nuel did not open. Staining of the spiral ganglion neurons was delayed. All the nervous structures of the cochlea were, however, stained at the end of the first postnatal month, as in normal animals, despite the irreversible complete deafness. Cholecalcin is thus present during development of the cochlea in both non-neuronal and neuronal structures, and is probably involved in very different processes in various types of cells.