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J Clos

Publications and source records attributed to J Clos.

At least 55 records · Page 3Linked to original sources
PubMed1989

Developing rat cerebellum--I. Effects of abnormal thyroid states and undernutrition on sulfated glycosaminoglycans.

Sulfated glycosaminoglycans deposition during rat postnatal cerebellar developmental is affected by altered thyroid states and undernutrition. These ontogenetic alterations seem not to be specific but to be one aspect of the general acceleration, slowing down and reduction of the cerebellar development occurring in thyroid-deficient, hyperthyroid and undernourished rats, respectively.

Aging↗
PubMed1989

Developing rat cerebellum--II. Effects of abnormal thyroid states and undernutrition on hyaluronic acid.

The early postnatal pattern of hyaluronic acid (HA) deposition in rat cerebellum is affected by thyroid deficiency, thyroxine treatment and undernutrition. The modification of HA ontogenesis apparently reflects the smaller number of cells formed in undernourished rats, or alterations of cell maturation (accelerated in thyroxine-treated and slowed down in thyroid-deficient rats). The developmentally regulated loss of tissue water is also affected in the three conditions; this can be correlated with the roughly simultaneous disappearance of extracellular, but not of total, HA.

Aging↗
PubMed1989

Developing rat cerebellum--III. Effects of abnormal thyroid states and undernutrition on gangliosides.

Alteration of rat postnatal cerebellar development produced by undernutrition, thyroxine treatment and thyroid deficiency also involves ganglioside deposition. The distribution of the different ganglioside types is apparently unaffected but quantitative alterations are present that reflect the reduction of cell number and cell process surface in the adult, and either acceleration or slowing down or reduction of cell formation and maturation occurring during cerebellar development in the three experimental situations.

Aging↗
PubMed1989

The cholinergic system in developing cerebellum: comparative study of normal, hypothyroid and underfed rats.

To overcome the deficiencies of previous findings, the activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were studied at very short age intervals to allow a more precise definition of the shape and timing of their developmental curves in normal, hypothyroid and underfed rats. In addition, AchE expression in developing cerebellum was studied histochemically in these three neurological models. When compared with structural findings in the literature, the results provide the following information on the normal and abnormal developing cholinergic system, related or not to cerebellar neurotransmission (1) AchE activity, unlike ChAT, can be considered as a good marker of the developing cholinergic archicerebellum. (2) ChAT and AchE are transiently expressed together in functionally noncholinergic Purkinje cells. In contrast with most regions of the central nervous system, the high ratio of ChAT to AchE activities in the early stage of cerebellar development suggests an enhanced synthesis of acetylcholine (Ach). The level of ChAT activity correlates with Purkinje cell size, supporting the concept of a neurotrophic role of Ach in early maturing macroneurons. (3) The archicerebellar cholinergic network appears to be relatively well preserved from undernutrition and, to an even greater extent, from hypothyroidism, compared to other systems of neurotransmission formed later and more widely distributed throughout the cerebellum. The presynaptic compartment seems to be more affected than the postsynaptic compartment. (4) In disagreement with some data in the literature, the abnormalities induced by both abnormal thyroidal and nutritional states were found to be irreversible.

Acetylcholinesterase↗
PubMed1989

Glycogenolytic responsiveness to glucagon, epinephrine, vasopressin and angiotensin II in the liver of developing hypothyroid rats. A comparative study of in vitro hormonal binding and in vivo biological response.

Both dose-response curves and time-courses of plasma glucose levels after single maximal doses showed that in vivo glycogenolytic responsiveness to glucagon and epinephrine was significantly higher in developing hypothyroid rats, whereas it remained unchanged after vasopressin and angiotensin II injections. In contrast with the decreased basal activity of phosphorylase(a), the glucagon-stimulated activity increased in hypothyroid rats, whereas it was only slightly modified under vasopressin stimulation. Daily thyroxine treatment abolished these abnormalities. Thus, there is a close correlation between glucose output and enzyme activation. The maximal binding capacity of [3H]vasopressin and [125I]glucagon was significantly decreased in hypothyroid rats, without changes in the apparent dissociation constant of hormone from its specific receptor. Daily thyroxine treatment also abolished this deficit, which moreover appeared to be independent of possible changes in plasma hormone levels. With respect to glucagon action, neither basal nor Gpp(NH)p-stimulated adenylate cyclase activities were affected in hypothyroid rats. Glucagon-sensitive adenylate cyclase activity and the apparent activation constant appeared to be unaffected. The apparent discrepancy between the results obtained from in vivo and in vitro experiments is discussed on the basis of different membrane transducing phenomena and related intracellular mechanisms underlying the biological response to hormonal stimulation.

Adenylyl Cyclases↗
PubMed1988

Studies on the 240-kDa Con A-binding glycoprotein of rat cerebellum, a putative marker of synaptic junctions.

A Con A-binding glycoprotein of Mr 240,000 was isolated from the remaining residue of rat cerebella after sequential extraction with buffers supplemented with or without neutral detergents. It was further purified by affinity chromatography on Con A-Sepharose in the presence of sodium dodecyl sulfate and preparative gel electrophoresis. This glycoprotein partially resists Triton X-100 extraction and is soluble in N-lauryl sarcosinate. The 240-kDa glycoprotein was not detected in kidney, liver, heart, forebrain and was specifically seen in cerebellar homogenate. The isolated glycoprotein appears to be similar, not necessarily identical with the GPA--a synaptic junction 240-kDa Con A-binding glycoprotein isolated from cerebellum earlier (Groswald and Kelly, J. Neurochem., 42 (1984) 534-546). Monospecific antibodies obtained against the purified 240-kDa protein were used for developmental study in normal and hypothyroid rats. There was observed an increase in the amount of 240-kDa glycoprotein, dependent on the age of the rat and this rise was in correlation with the synapse formation in rat cerebellum. The amount of 240-kDa glycoprotein is considerably reduced in hypothyroid rats.

Aging↗
PubMed1988

Comparative study of collecting tubules and vasopressin binding capacity in the renal medulla of developing hypothyroid rat.

The effects of congenital hypothyroidism on both the structure and function of the renal medulla were studied by comparing, in 1-month old rats, the structural features of collecting tubules with the capacity of vasopressin to bind membrane preparations and the related adenylate cyclase activation. With the exception of a reduced caliber, hypothyroidism had no effect on the density, total number, distribution of tubules according to epithelial thickness, or on the number of epithelial cells, or their area. The binding capacity of vasopressin and the related adenylate cyclase activation were equally reduced by about 50%, without changes in (i) the basal or guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, (ii) the apparent dissociation constant (KD) of labelled vasopressin from its specific receptor or (iii) the apparent activation constant (Kact) of vasopressin for adenylate cyclase. Taken together, these results clearly demonstrate that congenital hypothyroidism exerts a direct influence on the developing responsiveness of the renal medulla, mainly by reducing the density of active hormone receptors per cell, instead of reducing cell number or cell membrane area.

Adenylyl Cyclases↗
PubMed1987

Comparative study of the developmental patterns of vasopressin, glucagon, angiotensin II, and alpha 1-adrenergic receptors in the liver of developing and adult hypothyroid rats.

The effects of propylthiouracil (PTU) treatment on vasopressin, angiotensin II, glucagon and alpha 1-adrenergic receptors in both developing and adult rats were studied in liver membrane preparations by measuring the binding of the following ligands: [3H][8-lysine]vasopressin, [3H]Sar-angiotensin II, [125I]glucagon and [3H]prazosin, and in the case of glucagon, by measuring adenylate cyclase activation. Whatever the ligand used, in young as well as in adult animals, PTU treatment led to a similar reduction (about 50%) in the maximal number of binding sites (Bmax), without significant changes in the apparent dissociation constant (KD) of labeled hormone for its specific receptor. In normal adult animals, thyroxine treatment, i.e. hyperthyroidism, had an opposite effect on the Bmax (25-50% increase), without changes in the KD. In developing PTU-treated rats, the abnormalities completely disappeared after therapy with increasing physiological doses of thyroxine; consequently they were directly related to thyroid deficiency and not to toxic effects of PTU. Moreover, the abnormalities resulting from induced hypothyroidism were reversible. In developing and adult hypothyroid rats, neither basal, NaF-, nor Gpp(NH)p-stimulated adenylate cyclase activities were significantly affected. Glucagon-sensitive adenylate cyclase activity seemed to be slightly increased (by about 15%), without changes in the apparent activation constant (Kact). These results are considered in parallel with findings on plasmatic glucagon and vasopressin levels, compared with similar previous reports related to renal vasopressin receptors, and discussed with respect to unpublished observations concerning hepatic responsiveness to glycogenolytic hormones in young and adult rats with induced hypothyroidism.

Adenylyl Cyclases↗
PubMed1987

Effects of thyroid deficiency on the vasopressin receptors in the kidney of developing and adult rats. A comparative study of hormonal binding and adenylate cyclase activation.

The effects of propylthiouracil (PTU) treatment on renal vasopressin sensitive adenylate cyclase in young and adult rats were studied by measuring the binding of tritiated vasopressin and adenylate cyclase activation by vasopressin in kidney medulla plasma membranes. Thyroxine therapy completely corrected the effects of PTU treatment on the vasopressin-adenylate cyclase system. Thus, the abnormalities observed after a such treatment are directly related to thyroid deficiency and not to toxic effects of PTU. The inability of the kidney to normally concentrate urine in developing and adult animals with induced hypothyroidism was mainly related to the reduction of the number of binding sites without significant changes in the basal and guanylyl-imidodiphosphate (Gpp(NH)p)-stimulated adenylate cyclase activities, the apparent dissociation constant (Kbind) of labeled vasopressin from its specific receptor and the apparent activation constant (Kact) of vasopressin for adenylate cyclase. These results also show that thyroid deficiency has more effect on the ontogenesis of receptors than on their turnover, and demonstrate that a normal antidiuretic response occurs at very low receptor occupancy. Since, on the one hand, the hypothyroidism-induced abnormalities in renal medulla responsiveness to vasopressin were reversible and, on the other, only a permanent therapy consisting of two daily physiological doses of thyroxine from birth to the age of sacrifice fully restored them, the responsiveness of developing kidney to thyroid hormones appears to be fundamentally different from that of the CNS.

Adenylyl Cyclases↗
PubMed1987

A comparative study of plasma vasopressin levels and V1 and V2 vasopressin receptor properties in congenital hypothyroid rat under thyroxine or vasopressin therapy.

The effects of propylthiouracil (PTU) treatment on the plasma vasopressin level, on the number of hepatic (V1) or renal (V2) vasopressin receptors and on the hormone-sensitive adenylate cyclase activity in the kidney of developing rats were studied in parallel. In addition, we investigated the corrective effects of thyroxine therapy on the plasma vasopressin level and parameters related to the liver, and the effects of vasopressin therapy on the parameters related to the kidney. As already reported in the case of the number of V2 receptors and adenylate cyclase activity in the kidney, the deficient plasma vasopressin level in hypothyroid rats was completely corrected by two daily physiological doses of thyroxine given from birth to the age of sacrifice (1 month). Unlike the V1 receptors, the V2 receptors are known to be highly dependent on their specific circulating ligand. Since, first of all, the deficit was similar in the numbers of V1 and V2 receptors in hypothyroid rats, and, secondly, the treatment of hypothyroid rats by two daily physiological doses of long lasting vasopressin was found ineffective to recover the deficit in the number of V2 receptors, it can be concluded that thyroid deficiency directly alters vasopressin receptor biosynthesis in both liver and kidney, instead of acting via the depressed plasma vasopressin level.

Animals↗
PubMed1987

[Histological, biochemical and immunocytochemical data on the postnatal development of the hypothalamic magnocellular nucleus in the congenital hypothyroid rat].

1 The effects of congenital hypothyroidism on the postnatally developing hypothalamus and, particularly on the developing magnocellular nuclei and their vasopressinergic neurons, were studied by means of complementary approaches, such as histology, biochemistry and immunocytochemistry. 2 In normal rat, all the results show a precocious development of hypothalamus, and particularly of its magnocellular nuclei. 3 In hypothyroid rat, in showing that the nucleic acid and protein content of hypothalamus is diminished by the same magnitude than its wet weight, the results display a normal average cellularity and cell size. In the magnocellular nuclei of 10, 20 and 30 day-old rats, the neuronal density and cell size appear to be unaffected, except for the NSO at 35 days of age in which the two parameters are increased and decreased, respectively. With respect to vasopressinergic neurons in 35 day-old rats, their density and percentage in total cell population, as well as the axonal density are somewhat increased, the greater differences always significant being shown only in the NPV. Whatever the nuclei considered, the density of axonal varicosities does not differ from normal value. Finally, the vasopressin concentration of hypothalamus is significantly increased. Thus, it may be concluded that the mainly prenatal development of these vasopressinergic hypothalamic nuclei seems to be relatively spared from neo- and postnatal thyroid deficiency.

Animals↗
PubMed1986

The core promoter of mouse rDNA consists of two functionally distinct domains.

We have determined the sequences constituting the minimal promoter of mouse rDNA. A very small region immediately upstream of the transcription start site (from -1 to -39) is sufficient to direct correct transcription initiation. Sequences immediately downstream of the transcription start site (+1 to +11) increase the efficiency of transcription initiation. Point mutations within the core promoter have been generated and assayed for their effects on template activity and on interaction with the pol I specific transcription factor TIF-IB. The core promoter element appears to consist of two functionally different domains. The distal sequence motif from position -22 to -16 is recognized by factor TIF-IB. Mutations within this region lead to similar changes of both template activity and binding of TIF-IB. Two point mutations within the proximal sequence motif from -15 to -1 do not affect TIF-IB binding although they severely impair transcription initiation. It is suggested, that this proximal region plays a role in the assembly of functional transcription initiation complexes rather than in the primary binding of TIF-IB.

Animals↗
PubMed1986

A purified transcription factor (TIF-IB) binds to essential sequences of the mouse rDNA promoter.

A transcription factor that is specific for mouse rDNA has been partially purified from Ehrlich ascites cells. This factor [designated transcription initiation factor (TIF)-IB] is required for accurate in vitro synthesis of mouse rRNA in addition to RNA polymerase I and another regulatory factor, TIF-IA. TIF-IB activity is present in extracts both from growing and nongrowing cells in comparable amounts. Prebinding competition experiments with wild-type and mutant templates suggest that TIF-IB interacts with the core control element of the rDNA promoter, which is located immediately upstream of the initiation site. The specific binding of TIF-IB to the RNA polymerase I promoter is demonstrated by exonuclease III protection experiments. The 3' border of the sequences protected by TIF-IB is shown to be on the coding strand at position -21 and on the noncoding strand at position -7. The results suggest that direct binding of TIF-IB to sequences in the core promoter element is the mechanism by which this factor imparts promoter selectivity to RNA polymerase I.

Animals↗
PubMed1986

Ontogenesis of the kidney in the congenital hypothyroid rat. Biochemical and anatomical parameters of general development.

The effect of congenital thyroid deficiency upon the postnatal development of the rat kidney has been studied by measuring the nucleic acid, protein and lipid contents, and the area and thickness of the different regions in the organ, i.e. cortex, outer and inner medulla. Thyroid deficiency, induced by daily propylthiouracil treatment, strongly affects the development of the renal cortex. The medulla, and still more its inner part which develops early and partly before the onset of thyroid function, is relatively preserved. These effects are completely corrected by daily thyroxine therapy, excluding a possible toxic effect of the antithyroid drug. Moreover, they are partly reversible after cessation of propylthiouracil treatment.

Aging↗
PubMed1985

Con A-binding glycoproteins in the developing cerebellum of control and hypothyroid rats.

Concanavalin A (Con A)-binding glycoproteins were studied during the postnatal development of the cerebellum of control and hypothyroid rats. Only 4 glycoprotein bands have a transient behavior in control animals. They progressively increase until the 13th day and markedly decline between the 15th and the 18th postnatal day. In the cerebellum of hypothyroid rats, the level of these compounds is greatly reduced and the previous decrease observed in controls is not found again. This defect of Con A-binding glycoproteins mainly localized on the plasma membrane of parallel fibers might be related to the reduced synaptogenesis observed in the molecular layer of hypothyroid rats between parallel fibers and Purkinje cell dendritic spines.

Age Factors↗
PubMed1985

Response of the hypothalamo-neurohypophyseal axis (AVP system) and the kidney to salt load in young propylthiouracil-treated rats.

The development of the ability of the kidney to concentrate urine was studied in normal and propylthiouracil-treated rats by measuring urinary sodium concentration and osmolarity at different ages. It was shown that the normal animals, but not the PTU-treated ones were able to concentrate urine at 35 days of age. The response of the hypothalamo-neurohypophyseal axis (AVP system) and that of the kidney were investigated in the two categories of animals at 35 days of age by measuring concomitantly the AVP content of the hypothalamus and neurohypophysis, the AVP plasma concentration and the natremia and plasma osmolarity at various intervals after intraperitoneal injection of a 5% NaCl solution. In normal, as well as in PTU-treated rats, salt load did not lead to significant modifications of the hypothalamic AVP content. In comparison with normal rats, the neurohypophysis of the PTU-treated ones released AVP more slowly, but with a similar amplitude. In normal rats, the plasma AVP concentration was already maximal 30 min after salt load and then decreased and returned to the normal value at 2 hrs; at the same time, the natremia and plasma osmolarity also recovered their normal value. In contrast, the plasma AVP concentration as well as the natremia remained high 1 h 30 after salt load in PTU-treated rats. It is concluded that PTU-treated young rat is unable to compensate the salt load in normal delays. Beside the slowing in AVP release by neurohypophysis and decreased AVP plasma level, the responsiveness of the kidney seems to be altered.

Aging↗
PubMed1982

Influence of altered thyroid and nutritional states on early histogenesis of the rat cerebellar cortex with special reference to synaptogenesis.

On day of birth, the synaptic density of the rat cerebellar cortex in experimental, as compared to control, rats was slightly reduced or increased, respectively, after propylthiouracil treatment of the dam or thyroxine injection of the fetus. The stimulation of synaptogenesis in thyroxine-treated neonates was particularly obvious at the level of the ganglionic layer containing Purkinje cell bodies and was accompanied at the same level by accelerated growth of the presynaptic endings and perisomatic processes of the Purkinje cells. Undernourishment of the dam from day 6 of gestation led to an unexpected stimulation of synaptogenesis in the cerebellar cortex of the neonates; synaptic density was significantly increased above the normal value and much more markedly than in the thyroxine-treated neonates, but there was no abnormal proliferation of the neuronal processes. Different mechanisms underlay the transient stimulation of synaptogenesis in these two conditions. These results have been related to the disturbances in the development of Bergmann glia previously found soon after birth in altered thyroid and nutritional states.

Animal Nutritional Physiological Phenomena↗