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M J Burek

Publications and source records attributed to M J Burek.

10 recordsLinked to original sources
PubMed1999

Androgens rescue avian embryonic lumbar spinal motoneurons from injury-induced but not naturally occurring cell death.

The regulation of survival of spinal motoneurons (MNs) has been shown to depend during development and after injury on a variety of neurotrophic molecules produced by skeletal muscle target tissue. Increasing evidence also suggests that other sources of trophic support prevent MNs from undergoing naturally occurring or injury-induced death. We have examined the role of endogenous and exogenous androgens on the survival of developing avian lumbar spinal MNs during their period of programmed cell death (PCD) between embryonic day (E)6 and E11 or after axotomy on E12. We found that although treatment with testosterone, dihydrotestosterone (DHT), or the androgen receptor antagonist flutamide (FL) failed to affect the number of these MNs during PCD, administration of DHT from E12 to E15 following axotomy on E12 significantly attenuated injury-induced MN death. This effect was inhibited by cotreatment with FL, whereas treatment with FL alone did not affect MN survival. Finally, we examined the spinal cord at various times during development and following axotomy on E12 for the expression of androgen receptor using the polyclonal PG-21 antibody. Our results suggest that exogenously applied androgens are capable of rescuing MNs from injury-induced cell death and that they act directly on these cells via an androgen receptor-mediated mechanism. By contrast, endogenous androgens do not appear to be involved in the regulation of normal PCD of developing avian MNs.

Androgen Antagonists↗
PubMed1997

Sexually dimorphic neuron addition to an avian song-control region is not accounted for by sex differences in cell death.

Only male zebra finches sing, and several brain regions implicated in song behavior exhibit marked sex differences in neuron number. In one region, the high vocal center (HVC), this dimorphism develops because the incorporation of new neurons is greater in males than in females during the first several weeks after hatching. Although estrogen (E2) exposure stimulates neuron addition in females, it is not known where (E2) acts, or to what extent sexual differentiation influences the production, specification, or survival of HVC neurons. In the present study we first reassessed sex and (E2)-induced differences in cell degeneration within the HVC using the TUNEL technique to identify cells undergoing DNA fragmentation indicative of apoptosis. HVC neuron number, as well as the density and number of TUNEL-labeled and pyknotic cells within the HVC were measured in normal 20- and 30-day-old males and females, and in 30-day-old females implanted with E2 on posthatch day 18. Although HVC neuron number was greater in males than in females, and was masculinized in E2 females, no group differences were evident in the absolute number of dying cells. These results indicate that sex differences in cell survival within the HVC do not entirely account for sexually dimorphic neuron addition to this region. Rather, sexual differentiation acts on some HVC neurons before they complete their migration and/or early differentiation. Although the migratory route of HVC neurons is not known, a large number of E2 receptor-containing cells (ER cells) reside just ventromedial to the HVC and adjacent to the proliferative ventricular zone. Next, we investigated whether these ER cells contribute to early-arising sex differences in HVC neuron addition. By combining [3H]thymidine autoradiography with immunocytochemistry for ERs, we first established that ER-expressing cells are not generated during posthatch sexually dimorphic HVC neuron addition, and thus are not young HVC neurons that transiently express ERs during their migration. Furthermore, in 25-day-old birds we found no sex difference in the density of pyknotic cells among this group of ER cells, suggesting that these cells do not promote the differential survival of HVC neuronal precursors migrating through this region. Rather, ER cells or other cell populations may establish sex differences in HVC neuron number by creating dimorphisms in cellular specification.

Animals↗
PubMed1996

Programmed cell death in the developing nervous system.

Virtually all cell populations in the vertebrate nervous system undergo massive "naturally-occurring" or "programmed" cell death (PCD) early in development. Initially neurons and glia are overproduced followed by the demise of approximately one-half of the original cell population. In this review we highlight current hypotheses regarding how large-scale PCD contributes to the construction of the developing nervous system. More germane to the theme of this symposium, we emphasize that the survival of cells during PCD depends critically on their ability to access "trophic" molecular signals derived primarily from interactions with other cells. Here we review the cell-cell interactions and molecular mechanisms that control neuronal and glial cell survival during PCD, and how the inability of such signals to suppress PCD may contribute to cell death in some diseases such as spinal muscular atrophy. Finally, by using neurotrophic factors (e.g. CNTF, GDNF) and genes that control the cell death cascade (e.g. Bcl-2) as examples, we underscore the importance of studying the mechanisms that control neuronal and glial cell survival during normal development as a means of identifying molecules that prevent pathology-induced cell death. Ultimately this line of investigation could reveal effective strategies for arresting neuronal and glial cell death induced by injury, disease, and/or aging in humans.

Aging↗
PubMed1995

Estrogen promotes neuron addition to an avian song-control nucleus by regulating post-mitotic events.

Only male zebra finches sing and several telencephalic song control regions exhibit sex differences in neuron number that presumably reflect effects of estrogen (E2) exerted during the first few posthatch weeks. That is, implanting females with E2 during this time masculinizes neuron number and instills the capacity for vocal behavior. In certain song regions, E2 masculinizes neuron number by preventing the naturally-occurring death of neurons, long after their production, migration and process outgrowth are complete. However, in the Higher Vocal Center (HVC), the cellular mechanisms by which E2 establishes sex differences in neuron number are poorly understood. In contrast with other song regions, HVC neurogenesis overlaps with sexual differentiation and the incorporation of new neurons is greater in young males and E2-treated females, than in normal females. However, it is not known whether E2 promotes the addition of HVC neurons by stimulating their production, specification, and/or survival. To address this issue we injected males and females with [3H]thymidine on days 15 and 16 to label a small group of sexually dimorphic HVC neuronal cohorts born during sexual differentiation. Afterwards, on day 17, females were implanted with Silastic pellets filled with estradiol benzoate (EB) or left empty. We report here that EB exposure on day 17 masculinized (increased) the number of neurons in the HVC at day 35 that were labeled by [3H]thymidine injections on days 15/16. Thus, EB was able to increase cell number among at least some HVC neuronal cohorts after their final division, implying estrogenic regulation of post-mitotic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Initial sex differences in neuron growth and survival within an avian song nucleus develop in the absence of afferent input.

Only male zebra finches (Poephila guttata) sing, and nuclei implicated in song behavior exhibit marked sex differences in neuron number. In the robust nucleus of the anterior neostriatum (RA), these sex differences develop because more neurons die in young females than in males. However, it is not known whether the sexually dimorphic survival of RA neurons is a primary event in sexual differentiation or a secondary response to sex differences in the number of cells interacting trophically with RA neurons. In particular, since sexual differentiation of the RA parallels the development of dimorphisms in the numbers of neurons providing afferent input from the lateral magnocellular nucleus of the anterior neostriatum (IMAN) and the high vocal center (HVC), it has been hypothesized that sex differences in the size of these afferent populations trigger differential RA neuron survival and growth. To test this hypothesis, we lesioned either the IMAN or both the IMAN and HVC unilaterally in 12-day-old male and female zebra finches. Subsequently, RA cell death and RA neuron number and size were measured. Unilateral IMAN lesions increased cell death and decreased neuron number and size within the ipsilateral RA of both sexes. However, even in the IMAN-lesioned hemisphere, these effects were less pronounced in males than in females, so that by day 25 the volume, number, and size of neurons were sexually dimorphic in both the contralateral and ipsilateral RA. Similarly, the absence of both IMAN and HVC afferents did not prevent the emergence of sex differences in the number and size of RA neurons by 25 days posthatching. We conclude that these sex differences within the RA are not a secondary response to dimorphisms in the numbers of IMAN or HVC neurons providing afferent input.

Afferent Pathways↗
PubMed1994

Ontogeny of sex differences among newly-generated neurons of the juvenile avian brain.

In zebra finches, only males sing and brain regions controlling song exhibit sex differences in neuron number that stem from actions of estrogen during a critical developmental period. In certain song nuclei, these dimorphisms emerge long after neurogenesis and migration are complete, and estrogen promotes masculinization by preventing the death of well-differentiated neurons. But in another region, the higher vocal center (HVC), cellular mechanisms underlying sex differences in neuron number are not so well understood. In the HVC, neurogenesis continues throughout the post-hatch period of sexual differentiation, and sex differences arise during this time because neuron number increases in males but not females. We used [3H]thymidine autoradiography to establish when sex differences in neuron number first develop among a small group of HVC neuronal cohorts. We report that HVC neurons labeled by [3H]thymidine on days 15 and 16 after hatching are sexually dimorphic in number within 10 days of their birth, even before all cells in this cohort complete their migration and/or differentiation. This suggests that the cellular mechanisms contributing to sex differences in neuron number in the HVC may differ from those in other sexually dimorphic neural regions of the vertebrate nervous system. In addition, we found that although many thymidine-labeled HVC neurons ultimately project to the robust nucleus of the archistriatum (RA), a sexually dimorphic target, sex differences in their number develop before this efferent projection is established. These results have important implications regarding the site(s) of hormone action, since they suggest that sexual differentiation acts on certain HVC neurons before they establish their efferent projections, and perhaps even before they arrive within the HVC.

Animals↗
PubMed1992

Sex-dependent loss of projection neurons involved in avian song learning.

In zebra finches, only males sing, and the neural regions controlling song exhibit prominent, hormone-induced sex differences in neuron number. In order to understand how sexual differentiation regulates neuron number within one song nucleus, the lateral magnocellular nucleus of the anterior neostriatum (IMAN), we studied the development of sex differences among IMAN neurons that project to the robust nucleus of the archistriatum (RA). The IMAN is implicated in song learning, and previous ontogenetic studies have indicated that males lose over 50% of their IMAN neurons during the juvenile song learning period. Based on developmental changes in both the extent of androgen accumulation within the IMAN and its appearance in Nissl-stained tissue, it had been hypothesized that IMAN neuron loss was even greater in young females, resulting in sex differences in neuron number. However, this hypothesis has not been tested directly because the Nissl-stained boundaries of the IMAN sometimes are ambiguous in young animals, and are not evident at all in adult females. To circumvent these problems, we employed the retrograde tracer fast blue to study the development of IMAN neurons defined on the basis of their projections to the RA. We find that the number of these IMAN-RA projection neurons is much greater in adult males than in females, and that this sex difference develops during the juvenile period of sexual differentiation and song learning because a significant number of these neurons are lost in females but not in males. With respect to sexual differentiation, we conclude that masculinization (which is stimulated by the hormone estradiol) promotes the retention of IMAN-RA projection neurons. In addition, our results indicate that any loss of IMAN neurons that may occur in young males does not include cells projecting to the RA.

Aging↗
PubMed1991

Neuron loss and addition in developing zebra finch song nuclei are independent of auditory experience during song learning.

In zebra finches early auditory experience is critical for normal song development. Young males first listen to and memorize a suitable song model and then use auditory feedback from their own vocalizations to mimic that model. During these two phases of vocal learning, song-related brain regions exhibit large, hormone-induced changes in volume and neuron number. Overlap between these neural changes and auditory-based vocal learning suggests that processing and acquiring auditory input may influence cellular processes that determine neuron number in the song system. We addressed this hypothesis by measuring neuron density, nuclear volume, and neuron number within the song system of normal male zebra finches and males deafened prior to song learning (10 days of age). Measures were obtained at 25, 50, 65, and 120 days of age, and included four song nuclei: the hyperstriatum ventralis pars caudalis or higher vocal center (HVc), Area X, the robust nucleus of the archistriatum (RA), and the lateral magnocellular nucleus of the anterior neostriatum (IMAN). In both HVc and Area X, nuclear volume and neuron number increased markedly with age in both normal and deafened birds. The volume of RA also increased with age and was not affected by early deafening. In IMAN, deafening also did not affect the overall age-related loss of neurons, although at 25 days neuron number was slightly less in deafened than in normal birds. We conclude that while the addition and loss of neurons in the developing song system may provide plasticity essential for song learning, these changes do not reflect learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1981

A survey of adults' attitudes toward orthodontic therapy.

This study was designed to discover the nature of concerns that adult patients have toward their orthodontic therapy. I had observed, after many years of treating this age group, that concerns brought to my office by prospective and active patients were similar. All patients, however, felt that their attitudes and feelings were unique. Initially, the investigation was carried out in the presence of a psychologist during evening meetings. This was then followed by giving questionnaires to thirty-five patients. The first questionnaire was distributed to patients who had decided to undergo therapy but had not yet started. The second was given to that same group of patients upon completion, or imminent completion, of their treatment. Thirty-three patients returned both questionnaires. The principal conclusion was that negative concerns and fears that the patients had about their course of treatment were soon dissipated. Perseverance toward the treatment goal was an overriding characteristic of every patient, and satisfaction with the end result was uniformly favorable. These patients would encourage all others to undergo treatment if it was required.

Adolescent↗