3rd Postnatal Week Research Articles

Regional Differences in the Ontogeny of the Serotonergic Projection to the Cerebral Cortex

We used light and electron microscope immunocytochemistry to compare the development of the pattern of innervation and synaptic organization of the serotonin (5-HT) afferent system in sensory (visual and somatosensory) and motor areas of the rat cerebral cortex. Serotonin-labeled fibers were present in all cortical areas at birth appearing as two tangential streams, one above and one below the cortical plate. These fibers gradually arborized sending branches into all cortical layers in an “inside-out” sequence that broadly paralleled the gradient of neurogenesis and differentiation in the cortex. A striking feature at the early stages of postnatal development of the visual and somatosensory cortex was the transient presence of a dense accumulation of 5-HT fibers in layer IV. In agreement with earlier reports, transient aggregations of serotonergic axons characterized sensory but not motor areas of the cortex. The innervation pattern characteristic of the adult cortex was attained by the end of the 3rd postnatal week. Electron microscopic analysis of the developing visual cortex showed that 5-HT-containing axonal varicosities formed synaptic contacts, predominantly of the asymmetrical variety, throughout postnatal life. The proportion of varicosities forming synapses increased gradually from birth to reach a peak at the end of the 2nd week, then declined markedly in the subsequent week before rising again at later stages. It appears that the formation of exuberant synapses by 5-HT axons coincides with the period of maturation of the neuronal circuitry of this cortical area. When quantitative analysis was restricted only to layer IV, the proportion of varicosities forming synapses reached a peak at the end of the 1st week of life, when transient innervation was most prominent in this layer. These results suggest that the effects of this dense band of serotonergic axons may be mediated through axodendritic synapses. The types of postsynaptic elements involved in the formation of synapses varied according to age, suggesting progressive morphological differentiation of cortical target neurons or, alternatively, a continuous process of removal and establishment of new connections by 5-HT axons in the visual cortex. In contrast, analysis in the motor cortex revealed a continuous increase in the proportion of 5-HT varicosities engaged in synaptic contacts from birth to the late stages of development. The results presented here provide anatomical evidence for a differential role of 5-HT in the maturation of the cerebral cortex.

Chronic prenatal ethanol exposure alters the normal ontogeny of choline acetyltransferase activity in the rat septohippocampal system.

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) in the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1-22, pregnant rats were either fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting and an approximate 5-fold increase (septal area) and 7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair-fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet-stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system. The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system.(ABSTRACT TRUNCATED AT 250 WORDS)

Transplants Enhance Locomotion in Neonatal Kittens Whose Spinal Cords Are Transected: A Behavioral and Anatomical Study

We have studied the locomotor development of kittens that received complete low thoracic spinal cord transections and embryonic spinal cord transplants as newborns. Embryonic spinal cord (E21-E26) transplanted into the site of a transection integrated well with the host spinal cord and promoted the development of overground locomotion. Spinalized kittens with transplants were first distinguished from spinalized kittens during the 2nd and 3rd postnatal weeks when kittens with transplants positioned their hindlimbs underneath their bodies which promoted support of the hindquarters. By postnatal Week 6, kittens with transplants exhibited overground locomotion characterized by full weight support and moderate balance control. By 20 weeks of age, as many as 96% of the step cycles showed full weight support and as few as 2% of the step cycles were interrupted by a fall. Most kittens also showed coordination between the forelimbs and the hindlimbs. They differed from normal in the precocious onset of reflex stepping and in the less precise interlimb coordination and more precarious balance during overground locomotion. The overground locomotor performance of kittens with transplant greatly exceeded that of spinal kittens without transplants since few spinalized kittens showed any full-weight-supported step cycles and none showed coordination between the forelimbs and the hindlimbs. In the absence of a transplant, no fibers could grow across the lesion site. In the presence of a transplant, fibers grew across the lesion site and established anatomical connectivity with the host. Host segmental systems identified by the presence of calcitonin gene-related peptide- and substance P-immunoreactive fibers were found throughout the transplants. Descending host systems of supraspinal origin were identified by serotonin- and dopamine β-hydroxylase-immunoreactive fibers throughout the transplants. The growth of supraspinal axons into the transplant, and in one case into the caudal host spinal cord, provided a possible anatomical basis for the development of coordinated overground locomotion.

The surface evoked potential and parvalbumin-immunoreactivity in the somatosensory cortex of the developing rat.

The development of the rat somatosensory system was followed electrophysiologically and immunohistochemically. In the surface evoked potential elicited in the primary somatosensory cortex by electrical stimulation of the whisker C3 follicle, a short-latency positive wave was first recorded on postnatal Day 2. A long-latency positive wave was recorded in some pups on postnatal Day 7 and in most pups on postnatal Day 8. On postnatal Day 10, a P/N complex appeared between the short- and long-latency positive waves. Parvalbumin, believed to appear with functional maturation, appeared mainly after postnatal Day 7 in Layer V in the underlying area, although a few weakly stained cells appeared on postnatal Day 5. On postnatal Day 10, weakly stained cells appeared in the area containing barrels; their staining increased with time. In this system, electrophysiological and immunohistochemical parameters changed by the 3rd postnatal week with the most marked changes occurring within 2 postnatal weeks.

Psychomotor functions in developing rats: Ontogenetic approach to structure-function relationships

The functional development of the central nervous system (CNS) in the rat was studied from the 10th to the 45th postnatal day, through the ontogeny of psychomotor and sensory functions, by a battery of behavioral tests. The ontogenetic development of 10 different functions was described. The results showed that novelty-induced functions matured progressively in an adult-like pattern of functioning in the 3rd postnatal week. Indeed, exploratory activity was low at the 10th day, increased significantly to reach highest values from 20th to 30th postnatal day, then declined at the 45th postnatal day. No habituation was exhibited by 10- and 15-day-old rats; it appeared at the age of 20 days. Emotional reactivity induced by the novelty of surroundings clearly appeared from the 20th postnatal day, when the features of adult animal were reached. It appeared also that reflex and automatic motor functions came to maturity by the age of 3 wk, while voluntary motor functions continued to improve until the 30th day. Thus, the latency of the hind paw lifting reflex occurrence significantly decreased from the 10th to the 20th postnatal day, when the most improved values were reached. The wire-grasping times increased from the 10th to the 25th postnatal day in an exponential fashion. Locomotor activity developed significantly from the 10th to the 15th day, when the mature locomotion pattern was exhibited. The coordination of complex movements and motor initiative appeared only after the 20th postnatal day. The latencies of execution of crawling along the wire and of leap onto the ground decreased significantly from the 20th to the 45th day. These studies reveal the presence of the caudal to rostral sequence of CNS development, predicting a spatio-temporal functional maturation of nuclei and centers in the rat's CNS. The building of the time-sequence of regional maturation of the brain integrated activities was attempted.

The ontogeny of [3H]γ-hydroxybutyrate and [3H]GABA B binding sites: relation to the development of experimental absence seizures

γ-Hydroxybutyric acid (GHB) is a naturally occurring compound which has the ability to induce generalized absence seizures when given to animals. There is growing evidence that both γ-aminobutyric acid (GABA) B- and GHB-mediated mechanisms are involved in the pathogenesis of this phenomenon. Because of the fact that absence seizures are a disorder of children the ontogeny of [3H]GHB and [3H]GABA B binding and the developmental appearance of absence seizures in the GHB model of absence was ascertained and compared in developing rats. [3H]GABA B binding was present within the first 3 days of postnatal life and rose to levels which exceeded those found in adults, peaking between the 3rd and 5th postnatal week. [3H]GHB binding on the other hand did not appear until postnatal day 17 when it was detectable in the CA1 region of the hippocampus. There was a steady increase in [3H]GHB binding until adult levels were reached by postnatal day 40. Comparison of [3H]GABA B and [3H]GHB binding revealed that both sites were common to layer I–III of cortex, but otherwise differed in their regional distribution. There was an absolute concordance of the ontogeny of GHB-induced absence seizures with the developmental appearance of [3H]GHB binding in the superficial laminae of cortex; both appeared at postnatal day 18. These data support the hypotheses that the [3H]GHB and [3H]GABA B binding sites are separate from one another and suggest that maturational events in thalamus and cortex in the 3rd postnatal week are involved in the expression of GHB-induced absence seizures.

Developmental changes in the response of rat isolated duodenum to nicotine

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3×10 −7 to 10 −3 M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10 −6 to 10 −4 M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with α-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P 1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by α,β-methylene ATP, a stable P 2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.

Prognostic significance of spontaneous motility in very immature preterm infants under intensive care treatment.

Qualitative analysis of spontaneous motility was performed in 22 preterm infants (gestational age 25-31 weeks) on the intensive care unit. The infants were videorecorded once a week in the late afternoon during 1 h until 36 weeks of gestation. Quality of movement was analyzed by 8 observers using visual 'Gestalt perception' and compared with the neurological outcome 1 year after term. A normal quality of movement consistently predicted a normal neurological outcome with a probability of 90-100%. An abnormal quality of movement predicted an abnormal outcome with a probability of only 56% in the first, but with a probability of 82% in the third postnatal week. The average interobserver agreement was 78%. The analysis of spontaneous motility for the early diagnosis of neurological dysfunctions can reliably be applied on very immature preterms under intensive care conditions from the 3rd postnatal week on.

Preproenkephalin mRNA expression in the developing and adult rat brain

[Met 5]-Enkephalin is derived from the protein precursor, proenkephalin A, which in turn is encoded by the preproenkephalin (PPE) gene. [Met 5]-Enkephalin is not only a putative neuromodulatory substance, but also serves as a growth factor (= opioid growth factor, OGF). OGF exerts an inhibitory influence on the developing nervous system and is especially targeted to cell proliferative and differentiative events. This study examined the relationship of PPE mRNA expression to late prenatal and postnatal rat brain development. Northern blot analysis of the whole brain and cerebellum showed that message is present in the fetal nervous system on prenatal day 15 (the earliest timepoint examined), is expressed at relatively similar levels within each tissue during the first 2 postnatal weeks, and reaches adult levels by the beginning of the 3rd postnatal week. In situ hybridization methodology revealed that PPE mRNA was prominent in areas associated with cell generation. Message was found in sites of primary (i.e., ventricular region) and secondary (e.g., external germinal layer of the cerebellum) cellular replication, as well as in discrete foci of cell proliferation (e.g., medullary layer of the cerebellum). PPE mRNA was also present for varying periods of time in postmitotic cells. During development, a number of patterns (decrease, increase, and no perceptible change) of PPE mRNA could be detected in relationship to the fetal/neonatal period. Given the strong evidence (e.g., regulation of cell proliferation and differentiation, temporal and spatial patterns of peptide and zeta opioid receptor) that enkephalin immunoreactivity is associated with proliferating and differentiating neurons and glia, these results suggest that the source of [Met 5]-enkephalin is both autocrine and paracrine in nature.

Effects of weaning on phosphate transport maturation in the rat kidney. Clearance and brush border membrane studies.

Renal phosphate transport matures via an increase in the carrier affinity for phosphate during the 3rd post-natal week in the rat. This study examines whether weaning, which normally takes place during this period, plays a role in phosphate transport maturation. Early weaning (EW) and prevention of weaning (PW) both increased the fractional excretion of phosphate (EW 26.5 +/- 4.9, PW 26.7 +/- 2.2, controls 11.3 +/- 2.8, P < 0.001 and P < 0.05, n = 6 in each group). EW and PW also decreased the uptake of phosphate into brush border membrane vesicles (BBMV) isolated from the renal cortex of 21-day-old rats. Glucose transport in BBMV was not affected. The kinetics of phosphate uptake, measured in the presence of a sodium gradient, showed lower Vmax (4,112 +/- 362 pmol/mg protein per 10 s) in EW BBMV than in controls (6,030 +/- 200, n = 5, P < 0.001), but the affinity of the carrier for phosphate (1/Km) did not change. The decrease in Vmax may be due to the enhanced phosphate supply. The affinity of the carrier was lower in PW rats (Km = 0.31 +/- 0.04 mM) than in controls (0.18 +/- 0.04, n = 5, P < 0.01) but the Vmax remained unchanged. The low affinity may indicate that normal maturation of tubular transport, in which carrier affinity increases, is altered. The plasma concentrations of corticosterone, parathyroid hormone, insulin and triiodothyronine and their changes during EW and PW are also reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an early postnatal hypoxia on the development of spontaneous head movements in rabbits.

The early detection of minor brain dysfunctions resulting from perinatal hypoxia is very important since the prognosis of the affected children can be substantially improved by a prompt treatment. Therefore, this paper deals with the influence of an early postnatal hypoxia on the postnatal development of spontaneous head movements and the influence of the visual system on head movements in normal and hypoxic disturbed ontogenesis. Head movements were recorded in 12 unrestrained spontaneously behaving alert rabbits from 6 litters with the sensor coil technique. One rabbit of each litter was exposed to a single acute hypoxia (FiO2 = 0.05) for 3 h at the 1st day of life. The siblings were regarded as a control group. The most important characteristic of the postnatal development of the head movements is the forming of horizontal saccadic movements during the second postnatal week and their perfection by an increase in mean velocity up to the 20th postnatal day. The early postnatal hypoxia leads to a decrease of the mean velocity of saccadic head movements. But this is only true if the rabbits have open eyes. Blind-folding the rabbits of the control group during the recordings was followed by a decrease of the mean velocity (14th and 20th postnatal day) and the amplitude (at the 20th postnatal day) of the saccadic head movements. In contrast to the non-hypoxic rabbits, blind-folding had no perceptible influence on head movements in hypoxic rabbits until the 3rd postnatal week. Our results suggest that early postnatal hypoxia causes a

Refinement of dendritic arbors along the tonotopic axis of the gerbil lateral superior olive

We have investigated the development of dendritic arbors in a central auditory nucleus in the Mongolian gerbil, the lateral superior olive (LSO). The morphology of these arbors has been shown to vary with tonotopic position in adults, with high frequency neurons having a more restricted field. In the present study, qualitative observations were made on horseradish peroxidase-filled neurons from animals 1–11 days postnatal, and quantitative results were obtained from Golgi-impregnated material from animals 10 days postnatal and older. The tonotopic position of each cell was computed as a percent of the total distance along the LSO. The dendritic arbor high frequency neurons became spatially constrained along the frequency axis during the 3rd postnatal week, while those in the low frequency region retained a broader arborization into adulthood. This refinement was correlated with a decrease in total dendritic length and the number of branch points per neuron, particularly in the high frequency projection region. The distribution of octave bandwidths to which single LSO neurons responded in 13–16 day animals showed a similar course of maturation across the tonotopic axis: high frequency neurons responded to a larger number of octaves, and with greater variability, than those in adults. These data suggest that a specific alteration in dendrite morphology, which occurs after the onset of response to airborne sound, may contribute to adult frequency selectivity.

The development of the somatosensory representation in the superior colliculus of visually deprived mice

Mice were enucleated bilaterally at birth in order to investigate whether early visual deprivation had any influence on the development of the somatosensory representation in the superior colliculus (SC). Single unit recordings were performed during the 2nd, 3rd, 5th and 8th postnatal week in both normal and enucleated mice. It was found that, in visually deprived mice, there was a dramatic increase of the SC somatosensory units starting from the 3rd postnatal week, as occurs in normal mice. During the 5th and 8th postnatal week, this increase was larger than in normal mice, mainly due to the invasion of the somatosensory input into the superficial layers. In visually deprived mice, both the orientation of the somatosensory map and the magnification of some body parts, such as the upper vibrassae, did not show any difference with respect to normal mice. These results indicate the involvement of both vision-dependent and independent mechanisms in the formation of the SC somatosensory representation. In fact, whereas the segregation of the somatosensory afferents in the deep layers depended on the presence of visual input, the postnatal emergence and the topographic arrangement of the somatosensory map resulted to be independent of vision.

Development of glial fibrillary acidic protein immunoreactivity in thyroidectomized rats

The majority of astroglia develop postnatally in rats. GFAP (glial fibrillary acidic protein)-immunoreactivity appears mainly during the 2nd and 3rd postnatal weeks throughout the brain. Hypothyroidism inhibits, among others, the cell proliferation, maturation, and migration of neurons. However, hardly any data on the effect of hypothyroidism on GFAP-immunoreactivity are available in the literature. In our experiments, thyroidectomy was performed between the 3rd and 5th postnatal days. Operated and control animals from the same litter were perfused transcardially and processed for immunohistochemistry in parallel after 2, 3, and 4 wk. On the basis of serial sections, the development of GFAP-immunoreactivity was not generally affected by hypothyroidism. We could observe only two phenomena that showed a tendency of retardation in the operated animals: (1) the decrease of the strong GFAP-immunopositivity of white matter tracts (for example, internal capsule and pyramidal tract) and (2) the gradual disappearance of the GFAP-immunoreactive radial fibers (for example, in the neocortex, in the olfactory bulb, and around the 3rd ventricle).

The postnatal emergence of a functional somatosensory representation in the superior colliculus of the mouse

The somatosensory map of the superior colliculus was studied in the mouse during the 2nd and 3rd postnatal weeks, with particular attention to the representation of the vibrissae. The presence of an organized somatosensory projection was not electrophysiologically demonstrable until the beginning of the 3rd postnatal week, in coincidence with the opening of the eyes. Recordings performed during the 2nd postnatal week showed that the collicular units responding to tactile stimuli were rare and functionally immature. Starting from the beginning of the 3rd postnatal week, there was a dramatic increase of the number of somatosensory units and the appearance of an ordered topography, together with the maturation of the neuronal electrical properties. All the features of the adult collicular somatosensory map were found in the 3rd postnatal week, including the magnification of the vibrissae occupying the central portion of the visual field. The functional maturation of the collicular somatosensory map of the mouse is therefore a postnatal event which starts during the 3rd postnatal week, just after the opening of the eyes.

Development of the Stria vascularis in the Rat

The rat is an altricial animal and is thus a useful model for the study of auditory development. The endocochlear potential (EP) undergoes a rapid increase in magnitude from the end of the 1st week to the beginning of the 3rd postnatal week. The purpose of this study was to examine the ultrastructure of the developing stria vascularis in the rat pup in order to correlate functional changes with structural alterations. Rat pups of various ages underwent EP measurement under Rompun anesthesia. The cochleas were rapidly removed under deep pentobarbital anesthesia. The tissues were fixed in 2.5% glutaraldehyde and postfixed in 1.5% osmium tetroxide. Thin sections were viewed and photographed using a Hitachi H7000 transmission electron microscope. A series of distinct developmental changes were observed. Intermediate and basal cells became more distinct from one another, and basal cells became more elongated. Marginal cells underwent progressive development of basolateral infoldings. These cytologic changes may signal the development of ion transport mechanisms necessary for EP development.

Detection of Growth-Stimulating Activity in the Proximal Small Intestine during Weaning in the Suckling Rat

Adaptive changes in enzyme expression and cell proliferation occur in the small intestine of the suckling rat at the beginning of the 3rd postnatal week. This physiological adaptation can be modulated by factors including diet or glucocorticoids. We have previously described an intestinal growth-stimulating fraction derived from the remnant small bowel after resection and found that enteral nutrition is critical for its detection. In view of the similarity between the changes in cell proliferation that occur between 15 and 22 days postnatally and those immediately after resection, we sought to determine whether the small intestinal mucosa of the neonatal rat also contains a similar growth-stimulating fraction. Our results show that extracts of the proximal intestine prepared from 15-day-old rats do contain the growth-stimulating fraction. The activity was not detectable in maternal milk nor in the intestinal extract from 8-day-old rats. When the suckling rats were deprived of solid food, the activity was not detectable in the 15-day-old group. Gel filtration of the acidic extract on a G-25 Sephadex column revealed that the active component is made up of two molecular weight species (approximately 4,500 and 1,500 daltons) similar to that described in the proximal intestine of the postresectional model. These findings suggest that dietary factors may play a role in modulating the proliferative changes that occur at the time of weaning by way of the growth-stimulating fraction.

Ontogenesis of auditory fovea representation in the inferior colliculus of the Sri Lankan rufous horseshoe bat, Rhinolophus rouxi

This report describes the ontogenesis of tonotopy in the inferior colliculus (IC) of the rufous horseshoe bat (Rhinolophus rouxi). Horseshoe bats are deaf at birth, but consistent tonotopy with a low-to-high frequency gradient from dorsolateral to ventromedial develops from the 2nd up to the 5th week. The representation of the auditory fovea is established in ventro-medio-caudal parts of the IC during the 3rd postnatal week (Fig. 3). Then, a narrow frequency band 5 kHz in width, comprising 16% of the bat's auditory range, captures 50-60 vol% of the IC (Fig. 3c). However, foveal tuning is 10-12 kHz (1/3 octave) lower than in adults; foveal tuning in females (65-68 kHz) is 2-3 kHz higher than in males (62-65 Khz). Thereafter, foveal tuning increases by 1-1.5 kHz per day up to the 5th postnatal week, when the adult hearing range is established (Figs. 4, 5). The increase of sensitivity and of tuning sharpness of single units also follows a low-to-high frequency gradient (Fig. 6). Throughout this development the foveal tuning matches the second harmonic of the echolocation pulses vocalised by these young bats. The results confirm the hypothesis of developmental shifts in the frequency-place code for the foveal high frequency representation in the IC.

Ontogeny of glutamate decarboxylase and ?-aminobutyric acid immunoreactivities in the rat cochlea

gamma-Aminobutyric acid (GABA)-ergic efferent nerve fibers were studied during the postnatal development of the rat cochlea, using light microscopic immunocytochemical techniques. Antibodies against GABA and its synthesizing enzyme, glutamate decarboxylase (GAD), were used. Immunoreactivity to GAD is already present at birth (postnatal day 1) and could be found below the inner hair cells of the basal turn. Immunoreactivity progressively extends toward the apical turn until day 3. GAD-like immunoreactivity appears under the outer hair cells on postnatal day 15 and is only found in the upper part of the second turn and in the apical turn. The distribution of GABA-like immunoreactivity closely corresponds to that observed with the anti-glutamate decarboxylase antibody. However, the GABA-like immunoreactivity appears about 1-2 days after GAD-like immunoreactivity. At the beginning of the 3rd postnatal week, an adult pattern of GABA- and GAD-like immunoreactivity is established. These results suggest that GABA, which appears under the inner hair cells largely before the onset of hearing, may play a neurotrophic function during cochlear maturation and participate in the regulation of the first cochlear potentials as soon as they appear.

Effect of Hormones and Development on the Expression of the Rat 1,25-Dihydroxyvitamin D3 Receptor Gene: Comparison with calbindin gene expression

We have used specific cDNAs to the rat vitamin D receptor (VDR) and to the mammalian vitamin D-dependent calcium-binding proteins (calbindin-D9k in intestine and calbindin-D28k in kidney) in order to obtain a better understanding of the regulation of the VDR gene and its relationship to calbindin gene expression. Hormonal regulation and development expression of the rat VDR gene were characterized by both Northern and slot blot analyses. Administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; 25 ng/day for 7 days) to vitamin D-deficient rats resulted in an increase in calbindin mRNA in intestine and kidney but no change in VDR mRNA in these tissues. Vitamin D-deficient rats responded to dexamethasone treatment (100 micrograms/100 g of body weight/day for 4 days) with a 2.5-fold increase in intestinal VDR mRNA which was accompanied by a 4-fold decrease in intestinal calbindin-D9k mRNA. Developmental studies indicated a pronounced increase in renal VDR mRNA and calbindin-D28k mRNA between birth and 1 week of age. In the intestine, an induction of VDR and calbindin-D9k gene expression was observed at a later time, during the 3rd postnatal week (the period of increased duodenal active transport of calcium). Taken collectively, our data indicate that in the adult rat, target tissue response to hormone is not modified by a corresponding alteration in new receptor synthesis. However, developmental studies indicate that the induction of 1,25(OH)2D3 receptor mRNA is correlated with the induction of calbindin gene expression. Our results also demonstrate that glucocorticoid administration can result in an alteration in intestinal calbindin and VDR gene expression.