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J R Brawer

Publications and source records attributed to J R Brawer.

64 records · Page 4Linked to original sources
PubMed1975

Relations between auditory nerve endings and cell types in the cat's anteroventral cochlear nucleus seen with the Golgi method and Nomarski optics.

Rapid Golgi impregnations of the ascending branches of the auditory nerve fibers and of the types of neurons in the anteroventral cochlear nucleus (AVCN) were studied. Entire ascending branches could be observed, some of these branches project to each subdivision, others do not. There are two main typesof large neurons: the bushy and stellate cells. Criteria were established for identifying unimpregnated bushy and stellate perikarya by means of Nomarski optics, and these criteria were checked by Momarski observations on neurons which had either impregnated dendrites and unimpregnated cell bodies or impregnated portions of perikarya. In this way, the relations of unimpregnated cell bodies to auditory nerve endings were observed. Furthermore, with Nomarski optics, the cytoarchitectonic subdivisions of AVCN could be determined. Differences in the end-bulbs and collateral endings formed by the auditory nerve fibers were distinguished in three of the cytoarchitectonic subdivisions of the AVCN. End-bulbs in the anterior division were much larger than those in the dorsal and ventral parts of the posterior division. The large end-bulbs of Held in the anterior division of the AVCN were consistently associated with the perikarya of bushy cells and not with those of stellate cells. The large end-bulbs are not observed in the posterior division. Thus, bushy cells in the posterior division, although morphologically similar to those in the anterior division, must have a different synaptic organization. This difference may correspond to electrophysiological distinctions in the time-patterns of response recorded in these regions following acoustic stimulation.

Animals↗
PubMed1975

Cytopathological effects of estradiol on the arcuate nucleus of the female rat. A possible mechanism for pituitary tumorigenesis.

Large subcutaneous doses (2 mg/21 days) of estradiol valerate (EV) given over several months will induce a prolactin and growth hormone-secreting pituitary tumor in female rats. The medial basal hypothalami (MBHs) of such EV-treated animals were examined at different time intervals with light and electron microscopes to determine whether EV affects the MBH and to relate any observed effects to the process of tumorigenesis. The MBHs of extensively treated rats exhibited profound glial and neuronal changes. The filament content of astrocytes was greatly increased and large dense pleomorphic inclusions filled both astrocytic perikarya and processes. Degenerating neuronal elements have been observed in the neuropil of extensively treated animals. Dark cells identified as M cells were seen to engage in phagocytosis and were loaded with dense inclusions. Some neurons in MBH contained large quantities of lipofuscin that was different in appearance from that of normal females of the same age. The glial reaction developed gradually. At earlier stages of EV treatment there were fewer reactive glia and these contained fewer inclusions. Myelin figures often occurred in these early inclusions. Reactive glia in EV-treated rats did not appear in the preoptic area, dorsomedial nucleus or lateral hypothalamus but were found in ventromedial nucleus. Retired breeders and starvation-stressed rats resembled normal controls. These pathological changes in MBH may result from a direct effect of EV on the hypothalamus. It is possible that, in addition to its effects on the hypophysis, EV suppresses or injures hypophysiotropic cells in MBH, thus releasing pituitary chromophobes from inhibitory hypothalamic influences. This could result in hypersecretion and neoplasia.

Animals↗
PubMedDate not supplied

The effects of oestrogen on hypothalamic tissue.

Oestrogens exert potent influences on hypothalamic differentiation and on sexual function throughout life. During the period in which the hypothalamus differentiates, the availability of oestrogens (or aromatizable androgens) to the hypothalamus results in a male pattern of gonadotropin secretion and in male sexual behaviour in the adult. Lack of oestrogens during this period results in a cyclic schedule of gonadotropin secretion and in female sexual behaviour. Oestrogens or their metabolites determine future sex-specific activity by facilitating synapse formation in developing target circuits. The onset of puberty may also in part reflect oestrogen-stimulated synapse formation in the hypothalamus. In contrast, oestrogen given to an adult female rat causes specific multifocal lesions in the lateral arcuate nucleus. Such animals exhibit persistent oestrus and small multicystic ovaries. Since the same anovulatory syndrome can be produced by mechanical disruption of neuronal pathways from more anterior regions to the arcuate nucleus, it would appear that oestrogen could effect a 'disconnection' of the circuit responsible for cyclic drive of gonadotropin secretion. Furthermore, old female rats spontaneously exhibit the same type of reproductive derangement as well as the arcuate lesion. Thus direct effects of oestrogens on neuronal circuitry within the hypothalamus may be responsible for (1) sexual differentiation, (2) the onset of puberty and sexual activity, and (3) cessation of reproductive function in the female rat.

Animals↗
PubMedDate not supplied

Estrogen-induced hypothalamic beta-endorphin neuron loss: a possible model of hypothalamic aging.

Over the course of normal aging, all female mammals with regular cycles display an irreversible arrest of cyclicity at mid-life. Males, in contrast, exhibit gametogenesis until death. Although it is widely accepted that exposure to estradiol throughout life contributes to reproductive aging, a unified hypothesis of the role of estradiol in reproductive senescence has yet to emerge. Recent evidence derived from a rodent model of chronic estradiol-mediated accelerated reproductive senescence now suggests such a hypothesis. It has been shown that chronic estradiol exposure results in the destruction of greater than 60% of all beta-endorphin neurons in the arcuate nucleus while leaving other neuronal populations spared. This loss of opioid neurons is prevented by treatment with antioxidants indicating that it results from estradiol-induced formation of free radicals. Furthermore, we have shown that this beta-endorphin cell loss is followed by a compensatory upregulation of mu opioid receptors in the vicinity of LHRH cell bodies. The increment in mu opioid receptors presumably renders the opioid target cells supersensitive to either residual beta-endorphin or other endogenous mu ligands, such as met-enkephalin, thus resulting in chronic opioid suppression of the pattern of LHRH release, and subsequently that of LH. Indeed, prevention of the neuroendocrine effects of estradiol by antioxidant treatment also prevents the cascade of neuroendocrine aberrations resulting in anovulatory acyclicity. The loss of beta-endorphin neurons along with the paradoxical opioid supersensitivity which ensues, provides a unifying framework in which to interpret the diverse features that characterize the reproductively senescent female.

Aging↗
PubMedDate not supplied

Steroidogenic enzyme activities in rat polycystic ovaries.

Ovaries containing multiple follicular cysts occur in a variety of anovulatory conditions. A macrocystic condition occurs spontaneously in rats following a single injection of estradiol valerate. The ovaries are small, and exhibit scant stromal tissue, few healthy follicles, and numerous large cystic and precystic follicles. We have also generated a microcystic condition by means of subcutaneous estradiol-containing silastic implants. These ovaries are large, and exhibit a stroma of hypertrophied lipid-filled cells, and numerous small cysts encircled by hypertrophied thecal cells. The macrocystic condition is associated with a uniformly attenuated plasma luteinizing hormone (LH) pattern, whereas large LH episodes characterize the microcystic condition. The marked dissimilarities between these two methods suggest that there may be corresponding differences in ovarian steroidogenic activity. We have measured the activity of enzymes involved in progestin and androgen biosynthesis in the two types of multicystic ovaries before and after LH - human chorionic gonadotropin (hCG) stimulation. Control ovaries were obtained at late proestrus from age-matched cycling animals. Radiometric enzyme assays for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD), C17,20-lyase (lyase), and aromatase were conducted on the microsomal fraction of ovarian homogenates. 3 beta-HSD activity was reduced by > 50% in both types of cystic ovaries compared with controls. There was a slight elevation in the 3 beta-HSD activity of macrocystic ovaries in response to hCG. 20 alpha-HSD activity was similar in controls and macrocystic ovaries but significantly lower (< 20% of control) in the microcystic ovaries. Lyase and aromatase activities were undetectable in cystic ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

20-Hydroxysteroid Dehydrogenases↗