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Biomedical subjects

J R Brawer

Publications and source records attributed to J R Brawer.

At least 55 records · Page 3Linked to original sources
PubMed1982

Early postnatal development of the arcuate nucleus in normal and sexually reversed male and female rats.

The ultrastructural characteristics of the arcuate nucleus in the rat were examined at days 2, 5, 10 and 15 postpartum in order to evaluate the cytological development of the nucleus during sexual differentiation of the hypothalamus. In an effort to accentuate potential steroid-dependent structural features, the nucleus in normal male and female rats was compared with that of rats in which sexual differentiation had been reversed, by subcutaneous injection of testosterone proprionate in neonatal female rats, and by bilateral castration of neonatal male rats. The arcuate nucleus did not reveal any evidence of sexual dimorphism nor any effects of neonatal castration or androgenisation. The nuclei of any animals exhibited an increase, with age, in morphologically mature neurons and synapses. At day 15, however, the nuclei still possessed features indicative of an immature neural system, including organelle-poor profiles of young neurons, growth cones, focal points of cellular degeneration, and a lack of myelinated axons and morphologically mature macroglial cells. Of particular interest was the observation that neonatally-castrated male rats failed to exhibit a quantitative increase in whorl bodies by day 15 post partum, in contrast to the characteristic increase in whorl bodies observed in male rats that were castrated in adulthood. The results indicate that the arcuate nucleus undergoes progressive structural maturation during sexual differentiation of the hypothalamus and that this development is not altered ultrastructurally by changes in the steroid environment. At day 15 postpartum, an age at which sexual differentiation is irreversibly fixed, the nucleus remains a partially developed neural system. Further structural maturation, both neuronal and glial, will undoubtedly contribute to changes in hypothalamic regulation of the pituitary-gonad axis which occur with age. The lack of whorl body proliferation in neonatally-castrated males indicates that the arcuate nucleus of developing animals does not respond morphologically to negative steroid feedback mechanisms in a manner comparable to that of adults. The proliferation of whorl bodies in response to steroid withdrawal is thus an age-dependent phenomenon.

Animals↗
PubMed1980

Insulin binding sites localized to nerve terminals in rat median eminence and arcuate nucleus.

Specific binding sites for blood-borne insulin were determined to be selectively localized on axons and axon terminals in the external median eminence and the hypothalamic arcuate nucleus by means of quantitative fine structural radioautography. This localization suggests that discrete populations of hypothalamic nerve terminals are potential targets for the direct effects of insulin and that insulin may act through synaptic mechanisms to influence hypothalamic circuits regulating energy balance and hypophyseal function.

Animals↗
PubMed1980

Effects of estradiol-induced lesions of the arcuate nucleus on gonadotropin release in response to preoptic stimulation in the rat.

Female Wistar rats treated with a single subcutaneous injection of 2 mg estradiol valerate (EV) develop gradually progressive, multifocal lesions of the arcuate nucleus. They also exhibit vaginal estrus and endocrine profiles characteristic of animals sustaining anterior hypothalamic deafferentation. In this study, EV-treated females with the arcuate lesions released significantly less LH 1 h following electrochemical stimulation of the medial preoptic area (MPOA) than did normally cycling controls in proestrus. FSH release in response to MPOA stimulation was the same for both groups. As plasma LH concentrations were not significantly different between EV-treated and control animals 1 h after the injection of a potent LHRH analog, the reduced LH response to MPOA stimulation appears to reflect a primarily hypothalamic defect. However, the EV treatment also affected pituitary responsiveness to long-term stimulation as evidenced by reduced LH responses to the LHRH analog after 2 and 3 h. No such differences were seen in the FSH response.

Animals↗
PubMed1980

Ovary-dependent degeneration in the hypothalamic arcuate nucleus.

The effects of estradiol valerate and constant light exposure on the histological appearance of the arcuate nucleus were assessed in female rats. Both of these treatments caused significant increases in the numbers of reactive microglial cells and astrocytic granules in the nucleus. Ovariectomy before either treatment prevented the glial reaction, indicating that the experimental manipulations triggered the secretion of an ovarian product which appears to be selectively toxic to the arcuate nucleus. The fact that monthly injections of estradiol valerate in male rats produced the same profile of degeneration in the arcuate nucleus suggests that the neuropathological agent may itself be estradiol. Ovariectomy also significantly reduced arcuate microglial reactivity associated with normal aging, which suggests that cyclic surges of endogenous estradiol may be capable of gradually producing an arcuate lesion. This phenomenon may accout for the hypothalamic reproductive failure associated with normal aging in the rat.

Animals↗
PubMed1979

Changes in the fine structure of tanycytes during the annual reproductive cycle of the male little brown bat Myotis lucifugus lucifugus.

The hypothalamic arcuate nucleus in the male little brown bat Myotis lucifugus lucifugus was studied with the electron microscope. Animals were killed by intracardial perfusion at each season throughout the year so that the arcuate nucleus could be examined for seasonal variations in morphology. Striking seasonal changes in the fine structure of ependymal tanycytes lining the arcuate nucleus were observed. Tanycytes in animals collected in the fall and early winter exhibited pale processes characterized by a scant internal framework of microtubules and fine filaments. These processes, which were found throughout the arcuate nucleus, exhibited simple irregular shapes. In animals collected between January and June, tanycyte processes contained dense accumulations of fine filaments intermingled with microtubules, and projected long attenuated extensions that often formed multilamellar sheets around axodendritic terminals or other neuronal elements. Tanycyte processes of animals collected in July and August were densely packed with microtubules and fine filaments. The processes radiated elaborate multilamellar extensions that encapsulated axons, dendrites and even entire neuronal perikarya. Multilamellar sheets consisted of as many as 10 or 12 closely spaced gyres. The seasonal variations in tanycyte structure are suggestive of astrocyte-like behaviour. These changes are discussed with respect to seasonal changes in hypothalamic neuroendocrine activity.

Animals↗
PubMed1979

Cytology of the arcuate nucleus in newborn male and female rats.

Five coronal levels of the arcuate nuclei in newborn male and female rats were examined with the transmission electron microscope. The nuclei from male and female neonates appear similar in all respects. All levels exhibit a significant population of round to oval cell profiles with large centrally located nuclei and scant cytoplasm which contains predominantly ribosomes, sparse mitochondria, and a few short cisternae of rough endoplasmic reticulum. These organelle-poor cell profiles resemble neuroblasts in other parts of the developing CNS. The arcuate nuclei of neonates also exhibit some cell profiles with the variety and quantity of organelles characteristic of mature neurons in the arcuate nuclei of adult rats. In addition, the neonatal arcuate nuclei show a paucity of synapses with apparent immaturity of those present, and numerous structures identified as growth cones. Definitive macroglia are not present in the arcuate nuclei of newborn rats.

Animals↗
PubMed1978

The effect of estrogens on hypothalamic structure and function.

Data accumulated from studies of several species indicate that sex steroids are metabolized by neuroendocrine tissues in a manner analogous to that of other target tissues. Evidence that androgens or their estrogenic metabolites affect the morphology and function of the nervous system in fetal, newborn, developing, and adult rats is presented. The destruction of neural processes subsequent to the administration of large doses of estrogen to intact rats can now be added to the previously known effects on synaptogenesis, cell morphology, and function. We believe this destruction to be a form of chemical deafferentation and that it may underlie age-related hypothalamic failure and the development of multifollicular ovaries in the rat. Implications for other species are not clear at present.

Adrenal Cortex Hormones↗
PubMed1978

Prolactin binding sites in the rat brain.

The principles of the competitive-binding assay were used in conjunction with light microscopic radioautography to demonstrate specific prolactin binding sites localized on ependyma of the rat choroid plexus, a previously unknown prolactin target tissue.

Animals↗
PubMed1978

Regional variations in glia and neuropil within the hypothalamic ventromedial nucleus.

The normal fine structure of glia and neuropil in the various regional subdivisions of the hypothalamic ventromedial nucleus in the adult male albino rat is described in this report. Although most HVM astrocytes throughout the nucleus appear ordinary in cytology, certain astrocytes found in the posterior ventrolateral subdivision of the nucleus appear somewhat reactive, in that they contain numerous thick fascicles of gliofibrils and pleomorphic dense bodies. The processes of these reactive astrocytes elaborate multiple, concentric lamellae which encapsulate small, round, pyknotic masses (probably degenerate axonal elements). These degenerate profiles, which are greatly outnumbered by normal HVM boutons, may represent synaptic contacts that deteriorate spontaneously in the normal adult HVM. Other signs of spontaneous degeneration occurring within this neuropil include the occasional presence of large masses of necrotic debris which appear engulfed by microglia. These findings suggest the presence in the normal adult HVM neuropil of a low-grade degenerative process with attendant gliosis, which is topographically centered about the posterior ventrolateral region of the nucleus. Regions of neuropil containing degenerate boutons also contain altered neuronal processes, some of which may be growth cones. The topographic proximity of the degenerating boutons to possible signs of axonal or dendritic regeneration indicates that certain synaptic circuits in the normal adult HVM may be plastic, and subject to spontaneous remodelling.

Animals↗
PubMed1978

Early postnatal development of ependyma in the third ventricle of male and female rats.

Ependyma in the third ventricle of developing male and female rats (0, 5, and 10 days postpartum) were compared with those of sexually mature male rats by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). No sexual dimorphism appeared in the developmental group. At all ages the dorsolateral ventricular wall was composed of ciliated ependymal cells, while ependymal cells of the ventrolateral wall exhibited apical microvilli and bleb-like irregularities. While SEM revealed similarities in apical morphology between ependymal cells adult and developing animals, TEM revealed marked differences between these cells. Many ciliated ependymal cells in developing animals resembled those of the adult while other neonatal cell profiles suggested ciliogenesis. Adult male rats exhibited two distinct tanycyte populations. One population, characterized by elaborate intercellular interdigitations and basal processes containing predominantly fine filaments, occurred adjacent to the ventromedial nucleus (VMN). The second population, characterized by less extensive intercellular interdigitations and basal processes containing, primarily microtubules, lined the roof of the lateral recess adjacent to the arcuate nucleus. Many tanycytes at the level of the arcuate nucleus in developing rats resembled closely those of the adult. In contrast, developing ependymal cells at the level of the VMN differed differed from their adult counterparts in that they exhibited little intercellular interdigitation and projected basal processes characterized by an internal framework of microtubules. Similarities in cytology between developing and adult tanycytes of the arcuate region suggest that the adult function of this population may be operative in the early postnatal period. In contrast, the differing cytology between adult and developing tanycytes of the VMN region suggests that the function of these cells is age-dependent.

Animals↗
PubMed1978

Effects of a single injection of estradiol valerate on the hypothalamic arcuate nucleus and on reproductive function in the female rat.

Young adult cyclic female rats were each injected with 2 mg estradiol valerate (EV) in sesame oil. Controls received an equivalent volume of sesame oil. Within 2 months after injection, most of the EV-treated animals showed persistent vaginal estrus and small polyfollicular ovaries as well as pathological changes in the hypothalamic arcuate nucleus. This pathological process was gradually progressive such that by 6 months after EV injection, the basal lateral region of the nucleus contained numerous reactive microglia, astrocytes, and degenerating elements of the neuropil. The experimental rats had elevated plasma PRL and GH concentrations which gradually diminished. Plasma estradiol concentration remained elevated 2 months after injection, while plasma LH and FSH concentrations stayed within the high and low normal range, respectively. The pituitary glands of injected animals weighed significantly more than those of controls 5.5 months after injection, but the enlarged glands did not cause hypothalamic compression. As mechanical anterior deafferentation of the medial basal hypothalamus has previously been shown to produce similar endocrine and reproductive alterations, it may be that estradiol treatment results in a functional-anatomical disconnection of the arcuate nucleus from the more anterior hypothalamic areas that regulate cyclicity. Whether this type of functional-anatomical phenomenon underlies other varieties of induced or secondary acyclicity in females remains to be determined.

Animals↗
PubMed1976

Localization of LHRH in neurons in frog brain (Rana pipiens and Rana catesbeiana).

Hypothalamic extracts from frogs (Rana pipiens) were found to contain a significant quantity of immunoreactive LHRH (3.27 +/- 0.63 ng/hypothalamus) (mean +/- SE) measured by radioimmunoassay. In additional radioimmunoassay studies of gross brain LHRH distribution in R. pipiens and R. catesbeiana, 16% of the total frog brain LHRH was located within the telencephalon-septum-optic chiasm regions while the remainder was distributed within the infundibular hypothalamic-pituitary complex. Immunohistochemical studies using the peroxidase-anti-peroxidase (PAP) unlabeled antibody enzyme technique demonstrated the presence of LHRH selectively within some neuronal perikarya located primarily in the median septal nucleus. Fibers containing immunoreactive LHRH were seen in the vicinity of these neuronal cell bodies and in the medial and lateral septal nuclei. In addition, LHRH-containing fibers extended to the median eminence and posterior pituitary, transversing a course beneath the preoptic recess or through the medial forebrain bundle, and then through the lateral infundibular hypothalamus to enter the median eminence bilaterally. LHRH within the median eminence was located in both the inner subependymal and outer glandular zones. On the basis of earlier physiological studies, it is proposed that this LHRH-peptidergic septo-infundibular pathway is involved in control of cyclic gonadotropin activity in the frog.

Animals↗