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ABSTRACT: The accessory olfactory bulb (AOB) is the first neural integrative center for the olfactory-like vomeronasal sensory system. In this article, we first briefly present an overview of vomeronasal system organization and review the history of the discovery of mammalian AOB. Next, we briefly review the evolution of the vomeronasal system in vertebrates, in particular the reptiles. Following these introductory aspects, the structure of the rodent AOB, as typical of the well-developed mammalian AOB, is presented, detailing laminar organization and cell types as well as aspects of the homology with the main olfactory bulb. Then, the evolutionary origin and diversity of the AOB in mammalian orders and species is discussed, describing structural, phylogenetic, and species-specific variation in the AOB location, shape, and size and morphologic differentiation and development. The AOB is believed to be absent in fishes but present in terrestrial tetrapods including amphibians; among the reptiles AOB is absent in crocodiles, present in turtles, snakes, and some lizards where it may be as large or larger than the main bulb. The AOB is absent in bird and in the aquatic mammals (whales, porpoises, manatees). Among other mammals, AOB is present in the monotremes and marsupials, edentates, and in the majority of the placental mammals like carnivores, herbivores, as well as rodents and lagomorphs. Most bat species do not have an AOB and among those where one is found, it shows marked variation in size and morphologic development. Among insectivores and primates, AOB shows marked variation in occurrence, size, and morphologic development. It is small in shrews and moles, large in hedgehogs and prosimians; AOB continues to persist in New World monkeys but is not found in the adults of the higher primates such as the Old World monkeys, apes, and humans. In many species where AOB is absent in the adult, it often develops in the embryo and fetus but regresses in later stages of development. Finally, new areas in vomeronasal system research such as the diversity of receptor molecules and the regional variation in receptor neuron type as well as in the output neurons of the AOB and their projection pathways are briefly discussed. In view of the pronounced diversity of size, morphologic differentiation, and phylogenetic development, the need to explore new functions for the vomeronasal system in areas other than sexual and reproductive behaviors is emphasized.
Microscopy Research and Technique 01/1999; 43(6):476-99. · 1.79 Impact Factor
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ABSTRACT: The mere appearance of a tubular, epithelially-covered, bilateral structure, no matter how minuscule, on the anteroventral nasal septum of tetrapods, is generally called the vomeronasal organ (of Jacobson). However, considering the functionality of this chemosensory structure, the presence of a non-cilated (microvillar) neuroepithelium (and not just any odd type of epithelium) encased in a variously shaped vomeronasal cartilage, along with vomeronasal nerve bundles and above all an accessory olfactory bulb connected to the limbic vomeronasal amygdala, are the absolute essential neurostructural characteristics and anatomic requirement for a functional VNO and the accessory olfactory system in any tetrapod. The distribution of the vomeronasal organ is reported here in two mammalian orders: Chiroptera and Primates. An impressive data pool on the vomeronasal organ of bats is now available, pointing to the fact that at this time bats may be the only group in which this organ system is extremely variable, ranging from total absence (even in the embryo) to spectacular development with numerous intervening stages in different chiropteran species. Of the eighteen bat families, only one family of New World leaf-nosed bats, family Phyllostomidae, exhibits functional vomeronasal organs. The vespertilionid bat Miniopterus, and the mormoopid bat Pteronotus, present exceptions to this rule. Among Primates, very few species have been rigorously studied. As a result, developmental variability of the vomeronasal organ is almost unknown; either the vomeronasal organ is well developed (such as in New World monkeys) or absent (as in Old World monkeys and great apes) in the adult. The concept whether adult humans or embryonic and fetal forms are endowed with this so-called sixth sense, is a controversial one and is under intense study in our laboratory and by others. The general phylogenetic implications based on our cladistic analysis of bats are that the vomeronasal organ complex has evolved several times. Among the prosimians and platyrrhine primates, the organ is well developed, although to a varying degree. Among catarrhine primates, its loss has occurred only once, as it is generally absent in the adult forms.
Microscopy Research and Technique 01/1999; 43(6):465-75. · 1.79 Impact Factor
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ABSTRACT: The aims of this study on the human olfactory bulb were two. First morphometry of the bulbs revealed marked declines during aging in the numbers of mitral cells and glomeruli, the bulb's principal integrative and relay elements. Numbers of glomeruli and mitral cells in each bulb of the young adult human were found to be approximately 8,000 and 40,000, respectively; these numbers declined steadily with age at an approximate rate of 10% per decade, so that in the ninth and tenth decades less than 30% of these elements remain in place. Such a marked decline with aging is suggested to underlie in part the decline in olfactory abilities (odor detection and identification) of humans with aging. In a separate study a systematic search for presence of an accessory olfactory bulb in the adult and aging bulbs was undertaken. No positive evidence for such an organized formation was found in the various regions of the adult bulbs of different age groups. The implications of these negative findings for the recent theories on human vomeronasal function and pheromonal perception are discussed.
Annals of the New York Academy of Sciences 12/1998; 855:708-15. · 3.15 Impact Factor
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ABSTRACT: Neurogenesis and proliferation of olfactory receptor neurons (ORNs) in the olfactory epithelium (OE) are reduced in postnatal hypothyroid rats and upregulated following restoration of thyroid function, leading to compensatory growth and restitution of these deficits [Paternostro M.A. and Meisami E. (1993). Dev. Brain Res. 76, 151-161; Paternostro M.A. and Meisami E. (1994). Dev. Brain Res. 83, 151-162]. To investigate thyroid hormonal role on maturation of ORNs, serial sections of the septal OE from normal newborn, 25- and 90-day-old rats were immunostained for olfactory marker protein (OMP), a marker for mature ORNs, and compared with the same from age-matched hypothyroid rats and those allowed to recover from thyroid deficiency at the time of weaning (day 25). The parameters studied were the localization and distribution of the OMP(+) cells within the OE and their density and total number. Hypothyroidism was induced by adding the reversible goitrogen propylthiouracil (PTU) to the rats' drinking water (1 g/l) from birth to days 25 or 90. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25. The OMP(+) cells occupied a distinct, broad band in the normal rat OE, while in hypothyroid animal, this band was narrow and restricted to OE's apical zones. Recovery resulted in broadening of the OMP(+) cell band and normalized distribution of OMP(+) cells as evident in the 90-day-old recovery animals. In normal control rats, density of OMP(+) cells increased by 2.5- and 1.3-fold during the suckling and post-weaning period (days 25-90), while total numbers of these cells increased by 12- and 3-fold, respectively, during the same age periods. Hypothyroidism decreased the growth in density by 25 and 30%, while total number of OMP(+) neurons were reduced by 40 and 70% in the 25- and 90-day-old animals, respectively. Withdrawal of PTU resulted in marked restoration of these deficits so that, at 90 days, the total number of OMP(+) cells were only 20% less than 90-day-old controls. These results indicate that thyroid hormones are essential for maturation of single ORNs and accretion of new mature ORNs in the OE of suckling and post-weaning rat. Also, the process of maturation and the final number of mature ORNs show remarkable recovery from hypothyroid-induced growth retardation.
International Journal of Developmental Neuroscience 12/1996; 14(7-8):867-80. · 2.42 Impact Factor
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ABSTRACT: Our recent studies have shown that restoration of thyroid function in developing hypothyroid rats results in upregulation of olfactory neurogenesis and compensatory proliferation of olfactory receptor neurons (ORN) in the olfactory epithelium (OE) (Paternostro and Meisami, Dev. Brain Res., 76 (1993) 151-161; ibid., 83 (1994) 151-162). It was not clear, however, whether the newly forming ORNs undergo complete maturational stages. To determine the effects of restoration of thyroid function on maturation of ORNs, the density and total number of mature ORNs were estimated in the OE of euthyroid and hypothyroid rats at postnatal days 1, 12, 25 and 90 and the results were compared with those in rats allowed to recover from early thyroid deficiency at weaning (day 25). As a marker for mature ORNs, and on the basis of one olfactory dendritic knob per ORN, the density and total number of the olfactory knobs were determined in the entire extent of the OE covering the nasal septum. Hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water (1 g/l) from birth until days 12, 25 or 90 of age. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25, leading to restoration of thyroid function and somatic growth recovery. The density of olfactory knobs was determined in 1 microm semi-thin sections stained with toluidine blue. In the normal rats, the number of olfactory knobs (= mature ORNs) increased 8.5- and 3-fold during postnatal days 1-25 and 25-90 respectively, reaching a mean value of 4 X 10(6)/septal OE, compared to 2.8- and 1.4-fold, respectively, for the hypothyroid rats. This led to deficits of 51% and 76% in the number of mature ORNs in the 25- and 90-day-old hypothyroid rats. In rats allowed to recover, the number of mature ORNs increased 4.5-fold during postnatal days 25-90 (3 X > hypothyroid rats and 1.5 X > controls). The results indicate marked upregulation of the maturational process of the ORNs and their compensatory accretion within the OE of the recovery group. The recovery process was not complete however, as indicated by a remaining deficit of about 25% in the total number of mature ORN, compared to normal 90-day controls. Thus thyroid hormones are essential for accretion of new mature ORNs in both the suckling and postweaning rats. Also, the ORNs show a remarkable ability to recover from severe early hypothyroid-induced growth retardation and attain normal mature state.
Developmental Brain Research 10/1996; 96(1-2):173-83. · 1.78 Impact Factor
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ABSTRACT: We recently reported that postnatal hypothyroidism results in marked reduction in surface area and cell number in the rat olfactory epithelium (OE) and recovery from this condition is accompanied by compensatory growth and restitution of these parameters. To explore the correlative changes in olfactory neurogenesis, i.e. mitotic activity of basal cells (BCs) and migration and survival of developing olfactory receptor neurons (ORNs), hypothyroid rats at postnatal (P) days of P10, P25 and P75 were injected with [3H]thymidine and OE was examined by quantitative autoradiography to determine the density of labeled nuclei at the BC and ORN zones at days 1, 5 and 15 post-injection. These data were compared with those of age-matched controls as well as young adult rats allowed to recover from hypothyroidism at the end of the suckling period (P25). Hypothyroidism was induced by administration of propylthiouracil (PTU) from birth in the drinking water (1 g/l) for 10, 25 and 90 days; recovery was induced by withdrawal of PTU at P25. The results indicated that the densities of labeled nuclei in the BC and ORN zones were not significantly altered in the suckling hypothyroid rats. In the P75 hypothyroid rats density of labeled BC nuclei was unaffected 1 day after injection but was significantly (36%) more than controls 5 days after injection; the density of neuronal nuclei in the ORN zone of P75 injected rats was markedly and significantly reduced (56% and 37% at 5- and 15-days post-injection). Data indicate that mitotic activity of BCs and their migration into the ORN zone is not affected in the hypothyroid infant rats but migration and/or survival of developing ORNs are markedly reduced in the postweaning growing rats made hypothyroid from birth. In rats allowed to recover from hypothyroidism at P25 and injected with labeled thymidine at P75, the density of labeled BC nuclei were significantly increased (48% and 43% at 1- and 5-days post-injection) compared to normal rats suggesting elevated levels of neurogenesis; density of ORN nuclei, however, were the same as controls. The results indicate critical regulatory influences of thyroid hormones on olfactory neurogenesis in the rat olfactory receptor sheet, in particular during the postweaning period.
Developmental Brain Research 01/1995; 83(2):151-62. · 1.78 Impact Factor
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ABSTRACT: Testicular weight and DNA content were markedly reduced (63 and 69%) in weanling Long-Evans rat pups rendered hypothyroid from birth by administration of propylthiouracil (PTU), a reversible goitrogen. These growth deficits worsened to > 80% by continuing hypothyroidism beyond weaning, to days 50 and 90. Recovery of thyroid function, brought about by discontinuing PTU at weaning, resulted in a paradoxical stimulation of testis growth, amounting to increased weight (40%), DNA content (60%) and size by 90 days, compared to age-matched controls. In the 25-day or older hypothyroid rats, testicular structure was immature and spermatogenesis markedly delayed, as evident by closed lumen and significantly reduced diameter of seminiferous tubules (38%), thickness of germinal layer (70%), and number of primary spermatocytes (86%), compared to control. Hypothyroidism did not alter the number of tubules per testis cross section. In the 90-day recovery rats, numbers of seminiferous tubules were unchanged but tubular diameter was significantly (20%) larger than in controls and spermatogenesis appeared very active as indicated by significantly increased germinal layer thickness (22%) and total number and density of primary spermatocytes (55% and 40%). The results show that although postnatal hypothyroidism is deleterious for testicular growth and spermatogenesis, recovery from this condition leads to enhanced seminiferous tubular growth and spermatogenesis.
Cell and Tissue Research 03/1994; 275(3):503-11. · 3.11 Impact Factor
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ABSTRACT: To assess the effects of early thyroid deficiency, and recovery from this condition on growth and development of olfactory epithelium (OE), male Sprague-Dawley rat pups were rendered hypothyroid by addition of propylthiouracil (PTU) to their drinking water from birth. At weaning some rats continued to receive PTU while others ere allowed to recover by withdrawal of PTU. Body weights and plasma thyroxine levels were determined in all groups. At the ages of 25, 50 and 90 days, the OE of these hypothyroid and 'recovery' rats were compared with age-matched controls for surface area, epithelial thickness, density and total number of olfactory receptor neurons, basal cells and supporting cells, using morphometric and cell counting methods. Normal rats showed marked and highly significant increases in the OE surface area and olfactory neuron number (2.6- and 2.3-folds) during the post-weaning period. In the hypothyroid rats, body growth and thyroxine levels were severely suppressed. The OE in the 25-day-old hypothyroid rats showed more than 40% reduction in surface area and cell number, compared to controls, but mean epithelial thickness and surface density of cells were unchanged. In the post-weaning hypothyroid rats, the expansion of surface area was severely retarded, and increase in cell number ceased entirely. In rats allowed to recover by PTU withdrawal, by 90 days of age, body weight and size had markedly increased but had not caught up completely; however, thyroxine levels were restored to normal and the surface area and cell number in the OE had increased in a compensatory manner, completely restoring the deficiencies in OE growth, including surface area, numbers of receptor neurons, basal cells and supporting cells. The results indicate marked growth plasticity of OE in the post-weaning rats. This pronounced ability to recover from early growth retardation contrasts with that seen in central neural structures, and indicates the great potential of OE for use as a model neural system for the study of recovery from early damage and growth retardation.
Developmental Brain Research 01/1994; 76(2):151-61. · 1.78 Impact Factor
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ABSTRACT: Cytochrome oxidase staining selectively highlights the synapse-rich neuropil of olfactory bulb glomeruli. Detailed morphometric enumeration of glomeruli in cytochrome oxidase-stained sections from postnatally developing rats reveals that the entire adult population of glomeruli (2400/bulb) forms early in life, the process being complete by days 3-5 postnatal. Newborn's glomeruli range in diameter from a mean of about 50 microns to a maximum of about 70 microns and undergo a 3-fold increase in diameter and a 20-fold increase in volume during days 1-50 postnatal. The presence of the entire adult's glomeruli in the neonate calls for a serious revision of some current views on glomerular development and, given the critical roles of glomeruli as modules, the findings bear important implications for the organization of olfactory system and early development of olfactory functions.
Developmental Brain Research 03/1993; 71(2):253-7. · 1.78 Impact Factor
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ABSTRACT: The effects of various durations of postnatal hypothyroidism followed by recovery were studied on testicular growth in Long-Evans and Sprague-Dawley rats from birth to 7 months. Hypothyroidism was induced by adding propylthiouracil (PTU) in drinking water (0.1%, w/v). Recovery was induced by withdrawal of PTU. Testicular growth was reduced in rat pups by 20, 65 and 90% at days 10, 25 and 50. Upon withdrawal of PTU at weaning (25 days), testicular growth resumed and became compensatory; catch-up growth occurred by day 65. Paradoxically, testicular growth progressively increased, surpassing the control weights by 40, 50 and 100% at days 75, 90 and 210. Maximal testicular growth rate in the recovery group was 35% higher, occurred 2 weeks later and lasted 2 weeks longer than controls. Testes of rats subjected to prolonged postnatal hypothyroidism (60 or 120 days) also showed recovery and hypertrophy, amounting to nearly twice the normal maximal growth levels, after at least 6 months of recovery. Body weights of recovering rats remained always significantly below those of controls. When the suckling pups were exposed to short, week-long regimes of PTU treatment, only rats treated during the early postnatal weeks (days 1-8 or 9-16) had enlarged testes; PTU treatment during the late suckling period (days 17-24) or later had no effects. Total duration of hypothyroidism in the suckling period was positively correlated with testicular enlargement. The results indicate that hypothyroidism early in life is stimulatory to testicular growth, resulting in a paradoxical twofold increase in final testicular size which occurs even if hypothyroidism is prolonged. These effects occur similarly in different strains of rat with differing sized testes. It is suggested that there is a sensitive period for this effect, i.e. during the first 2 weeks after birth. The marked plasticity of testicular growth as shown by its recovery and hypertrophy, even after long periods of hypothyroid retardation, is unique in the body and may be a useful model for studying hormonal factors regulating testicular growth and for animal breeding and research into infertility.
Journal of Endocrinology 01/1993; 135(3):495-505. · 3.55 Impact Factor
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ABSTRACT: The role of thyroid hormones in the testis is unclear, although recent evidence indicates they may be important for testicular development. Here we describe a novel method for increasing adult testicular size in the rat by induction of transient hypothyroidism during neonatal life. Rats were treated with a reversible goitrogen, 6-propyl-2-thiouracil from birth to day 25 when treatment was stopped, allowing return to a euthyroid state. At days 90, 135, 160, and 180, wt and DNA content of the testis, epididymis, ventral prostate, seminal vesicle, and those of some nonreproductive organs were determined, as well as serum levels of testosterone (T) and thyroid hormones. Despite decreased body wts in 90-day and older 6-propyl-2-thiouracil-treated rats, testis wt was increased by 40% and 60% at 90 and 135 days, respectively; maximal increase (80%) occurred at 160 days. These wt increases were accompanied by proportional changes in DNA content. Significant enlargements were also seen in other reproductive organs, but they occurred after a time lag and were smaller in magnitude. Interestingly, serum T levels showed no increase at any age. Weight and DNA content of nonreproductive organs, like body wts, were less than controls at all ages but thyroid hormone levels were normal. Thus, transient hypothyroidism in neonatal rats is associated with lasting enlargements in the ultimate size of testis and other reproductive organs in the adult. These changes are not related to excess T levels. The results indicate early critical influences of thyroid hormones on growth and development of the reproductive system and suggest an experimental model for inducing lasting enlargements in testis and reproductive organs. The model may also be useful for studying regulation of reproductive growth and final size.
Endocrinology 08/1991; 129(1):237-43. · 4.46 Impact Factor
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ABSTRACT: In the preceding paper it was shown that transient neonatal hypothyroidism induced by treatment of rats from birth to day 25 with the goitrogen 6-propyl-2-thiouracil (PTU) is associated with increases in testis wt and DNA content of up to 80% during adulthood. The testis changes were accompanied by similar, though less marked, increases in the wt and DNA content of epididymis and accessory organs. The purpose of this study was to assess sperm production in these enlarged testes and measure changes in sperm reserves in the epididymis. Testes and epididymides were obtained from control rats or rats given PTU from birth to day 25 (designated "treated") at 90, 135, 160, and 180 days of age. Daily sperm production (DSP), efficiency of sperm production (DSP/g testis), and epididymal sperm reserves were measured in all animals. Compared to controls, DSP of the treated rats was increased by 83%, 86%, 136%, and 132% at 90, 135, 160, and 180 days, respectively. Thus, in the treated rats, DSP, like testis wt, plateaued at day 160. In addition, efficiency of sperm production was increased by 15%-30% at all ages in treated animals. Epididymal sperm reserves were also increased in treated rats at all ages, but the correlation between DSP and epididymal sperm reserves was weak. Sperm motility and concentration in caudal epididymal fluid of adult males treated from birth to day 25 with PTU were normal. These males were fertile and sired litters in which pup wt and pup number were normal. These results indicate that neonatal hypothyroidism in rats is associated not only with increased testis size but also with increased efficiency of sperm production, resulting in increases in DSP of up to 140% in these animals during adulthood. Maximal sperm production is reached at 160 days of age in treated rats (compared to 100 days in controls), coinciding with the attainment of final testicular size. This system represents the first experimental model in which such large increases in sperm production can be produced. The neonatal PTU treatment does not appear to impair fertility or alter sperm characteristics when these animals become adults and may be a useful system with which to study factors which normally regulate sperm production.
Endocrinology 08/1991; 129(1):244-8. · 4.46 Impact Factor
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ABSTRACT: To study quantitatively actions of thyroid hormones on maturation of olfactory receptor neurons (ORN), surface density and total number of receptor knobs (1 knob/ORN) were measured in 1 mu sections from septal olfactory epithelium of newborn, 12- and 25 day normal, hypo- and hyperthyroid rats. Hypothyroidism was induced by adding to drinking water n-propylthiouracil (0.1% w/v) from birth. Hyperthyroidism was induced by daily injection of pups with T4 (1-thyroxine, 0.3 microgram/g b.w., s.c.). Experimental pups showed all the signs of hypo- and hyperthyroidism. Between days 1-25, normal pups showed marked increase in surface area of septal olfactory epithelium (6x), total number (12x) and surface density (#/mm2, 2x) of mature ORNs. Thyroid deficient rats showed, by day 12, marked reductions in epithelial surface area and total number of mature ORNs; these and the surface density deficits became very pronounced by 25 day (30% area, 27% density, 47% # mature ORNs). Hyperthyroid rats, however, did not show an increase in any of these parameters over controls. Although total number of ORNs (mature and immature), as measured by number of nuclei, was also reduced in hypothyroid pups, surface density was not altered, indicating that maturation of ORNs, but not their local accretion is altered in thyroid deficiency. The results indicate that thyroid hormones are essential for normal proliferative expansion of olfactory epithelium and for maturation of ORNs postnatally. These actions of thyroid hormones are not increased or accelerated by excess T4 suggesting saturation of the hormone receptor system at the normal plasma level.
International Journal of Developmental Neuroscience 02/1991; 9(5):439-52. · 2.42 Impact Factor
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ABSTRACT: As part of a study of the development of olfactory function in the rabbit, a morphometric analysis of the olfactory epithelium in newborn and 30-day-old animals was carried out. Surface area, thickness and cell densities of the olfactory epithelium were compared in hematoxylin-eosin stained serial sections through the nasal cavities of 4 newborn and 3 weanling rabbits. While the basic structure of the olfactory cavity changed little with age, a large quantitative development in the epithelium was observed. The pattern of growth appeared uniform and resulted in a 3-fold increase in total surface area from about 1 cm2 per side in the newborn to about 3 cm2 in the weanling, and an increase in thickness from approximately 65 microns to about 90 microns. The increase in thickness was due mainly to a disproportionate, 5-fold increase in the number of olfactory neurons. This resulted in a total of about 32 million cells per side by day 30, and represented an increase in the ratio of neurons to basal cells of 7:1 to 10:1, and neurons to supporting cells of 2:1 to 4:1. While such an increase in the number of primary neurons presumably improves the animal's perceptual abilities, it nevertheless raises the question as to how perceptual constancy can be maintained during a period of such rapid neural change.
Cell and Tissue Research 11/1990; 262(1):89-97. · 3.11 Impact Factor
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ABSTRACT: In the rat neonate, as in other altricial young, olfaction, in contrast to vision and hearing, is functional at birth, being critically important in feeding, growth and other aspects of infant-mother interaction. Yet, olfactory sensitivity, i.e., the ability to detect odors at low levels, is poor in the newborn, improving dramatically in the first few postnatal weeks. To find a neural explanation for this phenomenon at the level of peripheral olfactory system, we present quantitative light microscopic data which reveal that during the suckling period of postnatal development the surface area of the olfactory receptor sheet and the total number of olfactory receptor neurons increase by about 8- and 12-fold respectively, being about 15 mm2 and 1.0 million on each nasal half of the newborn. Since the number of mitral cells, the principal relay neurons of the olfactory bulb, is already established at birth, at about 40,000 per olfactory bulb, it may be estimated that the convergence ratio of the olfactory neurons to mitral cells increases by more than 10-fold in the suckling period. We propose that the increased number of primary sensory afferent units and the higher convergence upon the central relay cells enhances the physiological capacities of the olfactory afferent pathway, increasing the opportunity for spatial summation and facilitation. The latter changes may lead to reduced olfactory thresholds and improved sensitivity with development. The relative contribution of these peripheral changes in enhancement of olfactory sensitivity during growth is discussed in the light of our knowledge on the developing olfactory system.
Developmental Brain Research 04/1989; 46(1):9-19. · 1.78 Impact Factor
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ABSTRACT: Light microscopic numerical and morphometric studies were conducted on the olfactory epithelium of postnatal normal and hypothyroid rats. The normal rat olfactory epithelium undergoes marked growth and development during the suckling period (days 1-25): thickness, 50%; area, x 8, total number of olfactory neurons, basal and supporting cells, x 10, x 11 and x 8, respectively. The effects of thyroid hormonal deprivation on these proliferative postnatal growth changes were studied by adding PTU (n-propylthiouracil, a reversible antithyroid goitrogen) to the litter's drinking water from birth to weaning (day 25). The general architecture of naso-olfactory cavities as well as the histology and thickness of the olfactory epithelium were unaffected in the hypothyroid pups. However, the surface area of the olfactory receptor sheet was reduced by 40%, the reduction occurring throughout the cavity, though not uniformly. The total number of olfactory neurons, supporting and basal cells were reduced by 33, 45 and 47%, respectively. These results indicate that the postnatal vertical accretion of olfactory neurons occurring across the epithelial thickness is unaffected in the hypothyroid pups, while the horizontal proliferation of neurons accompanying the expansion of the sheet's surface area is markedly reduced. The results suggest differential effects of thyroid hormones on these modes of proliferative growth and imply further that in addition to possible direct effects, the influence of thyroid hormones on developmental growth of the olfactory epithelial sheets may be secondary to effects on the underlying submucosal connective tissue.
International Journal of Developmental Neuroscience 02/1989; 7(3):243-55. · 2.42 Impact Factor
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ABSTRACT: Postnatal growth of skeletal muscle (m. gastrocnemius) was compared in rats under euthyroid, hypothyroid and hypothyroid-rehabilitated conditions. In normal (euthyroid) animals, gastrocnemius muscle grows significantly in terms of weight (150 x) from birth to the young adult and, in terms of total contractile myofibril protein (15 x) and myosin ATPase activity (10 x) between days 25 and 90. Rats made hypothyroid (with 0.1% w/v propylthiouracil, PTU) from birth show reduced growth. At 25 days (weaning), compared with euthyroid, muscle weight is only 25% of normal, and a similar reduction is found in total DNA, RNA, protein, myofibril protein, and myosin ATPase activity. These deficits, already significant by day 10, are more marked by day 50 due to the near arrest of growth. Hypothyroid rats allowed to recover by PTU withdrawal after day 25 (rehabilitated) undergo marked compensatory muscle growth. By day 90, muscle weight and protein content increase 50 x, DNA 7 x and RNA 17 x. Over this period, total myofibrillar protein and myosin ATPase increase 20-40 x, but are still below those of 90-day controls, suggesting that the severe growth retardation had not yet been fully compensated. Early thyroid deficiency drastically reduces the normal age-related growth of skeletal muscle and severely retards the development of contractile elements, affecting muscle hypertrophy (protein content) more than cell proliferation (DNA content). Rehabilitation compensates to a major degree for this growth retardation. These results underline the key role of thyroid hormones in regulating development and maturation of skeletal muscle throughout the preweaning and postweaning phases of growth.
Mechanisms of Ageing and Development 12/1988; 45(3):285-97. · 3.44 Impact Factor
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ABSTRACT: Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.
Developmental Psychobiology 12/1986; 19(6):537-53. · 2.98 Impact Factor
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ABSTRACT: Newborn female Long-Evans rats were divided into groups of normal, hypothyroid [0.1% propylthiouracil (PTU) a reversible antithyroid goitrogen in the litter's drinking water], and hypothyroid rehabilitated (PTU water from birth to day 25, normal water thereafter). The rats were tested for several adaptive behavioral tasks between 40 and 90 days of age. At day 50, serum concentration of TSH and thyroid hormones revealed no detectable amounts of T4 and a 10-fold increase in TSH in the hypothyroid rats. At the same age in the rehabilitated animals, TSH levels were still below normal, a deficit fully normalized by day 90. Normal 50-day-old rats responded to pain stress (electric footshocks) by a significant depression of serum T4 and elevation of T3 levels within 10 min of treatment, whereas the rehabilitated animals exhibited an opposite pattern of response, i.e., an increase in the circulating T4 and a decrease in T3. At 50 days of age, both hypothyroid and rehabilitated rats showed decreased exploratory activity and no habituation in the hole-board test, whereas the locomotor activity of the rehabilitated females was significantly higher than that of the normals. No differences were found in the scores of passive avoidance learning (one trial step-through) among the three groups. Similarly, the rate of acquisition of the active one-way conditioned avoidance response (CAR) of the hypothyroid and rehabilitated rats did not differ significantly from that of the controls. However, the hypothyroid rats required significantly more unconditioned stimuli (footshocks) to acquire CAR and showed longer response latency and less intertrial responses. Although the hypothyroid rats showed no extinction of CAR, the rehabilitated rats were capable of extinction to an extent indistinguishable from normal rats. But compared with the normal animals, the rehabilitated rats showed significantly higher intertrial activity during both the acquisition and extinction phases of CAR.
Developmental Psychobiology 10/1986; 19(6):537 - 553. · 2.98 Impact Factor
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ABSTRACT: Long-Evans male rats were made hypothyroid from birth by the addition of 6-N-propylthiouracil (PTU) to their drinking water (0.1%). A group of animals was rehabilitated beginning at postnatal day 25 by withdrawal of the PTU from the drinking water. Subsequently, the rats were tested for a variety of behavioral tasks. Serum concentrations of thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were determined by radioimmunoassay. At 50 days of age, PTU-treated rats had non-detectable levels of T4 but an eight-fold increase of TSH. In 50-day-old, neonatally hypothyroid but rehabilitated rats, serum TSH and T3 were normal, although T4 was still significantly lower. At 90 days of age, basal levels of TSH and thyroid hormones were normal in the rehabilitated rats, but thyroid hormone secretion in response to various types of neural stress was markedly altered. Comparison of passive avoidance learning revealed no significant alteration in the memory retention of either PTU-treated or rehabilitated animals. The 50-day-old, rehabilitated rats showed increased locomotor activity both in running-wheel and in hole-board tests; this hyperactivity, though markedly reduced, still persisted at day 90. In the early phase of rehabilitation (50 days of age), decreases in exploratory activity and lack of habituation occurred with the hole-board test; by the late phase of rehabilitation (90 days of age) these behavioral parameters had become normal. These results suggest generally longer periods of plasticity of the brain and better prospects for rehabilitation from neonatal cretinoid retardation than commonly believed. Specifically, the pituitary-thyroid system and neural mechanisms integrating adaptive behavior possess considerable capacity for spontaneous recovery from hypothyroidism; certain types of altered neuroendocrine and behavioral responses appear to be less amenable to rehabilitation or require longer periods for complete rehabilitation.
Psychoneuroendocrinology 02/1986; 11(1):91-103. · 5.81 Impact Factor
