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Biomedical subjects

C A Mason

Publications and source records attributed to C A Mason.

At least 19 recordsLinked to original sources
PubMed1998

Granule neuron regulation of Purkinje cell development: striking a balance between neurotrophin and glutamate signaling.

Granule neurons, presynaptic afferents of Purkinje cells, are potent regulators of Purkinje cell development. Purified Purkinje cells survive and differentiate poorly, whereas coculture with granule neurons enhances their survival and dendritic development. Here we investigate the role of neurotrophins in granule-Purkinje cell interactions. BDNF or NT-4 improves, but NT-3 or CNTF reduces, survival of isolated Purkinje cells. When granule neurons are present, however, BDNF or NT-4 treatment leads to Purkinje cell loss. This decrease is overcome by anti-BDNF or TrkB-IgG-blocking reagents or by CNQX, a non-NMDA glutamate receptor antagonist. Furthermore, BDNF increases the spine density on the surviving Purkinje cells. These results suggest that Purkinje cell survival and differentiation are context-dependent and require a balance between neurotrophin- and activity-dependent signaling.

2-Amino-5-phosphonovalerate↗
PubMed1998

Developmental regulation of mossy fiber afferent interactions with target granule cells.

In an in vitro model system based on purified target cerebellar granule neurons and explants of afferents, pontine mossy fiber afferents stop growing through contact-mediated mechanisms when they encounter granule neurons. Here we studied the developmental regulation of the stop signal posed by granule cells and the response of mossy fibers to the stop signal in two culture systems. Granule neurons presented in slices or as dissociated cells from postnatal day (P) 4 and P7 cerebellum were more potent in the arrest of P0 pontine neurites than younger (P0-P2) or older (up to P14) granule neurons. In contrast, pontine neurites at embryonic day (E) 18, during their period of normal growth toward the cerebellum, grew extensively on both cerebellar slices of all ages from P0 to P10 and dissociated P4 granule neurons. When E18 explants were maintained for 2 days before plating in medium conditioned by neonatal cerebellar cells, E18 pontine explants were rendered more responsive to the stop signal from P4 granule cells. These results indicate that the stop signal, and the response of afferents to it, are developmentally regulated. Moreover, factors within the target region may initiate these interactions.

Animals↗
PubMed1997

Growth cone form is behavior-specific and, consequently, position-specific along the retinal axon pathway.

Video time-lapse microscopy has made it possible to document growth cone motility during axon navigation in the intact brain. This approach prompted us to reanalyze the hypothesis, originally derived from observations of fixed tissue, that growth cone form is position-specific. The behaviors of Dil-labeled retinal axon growth cones were tracked from retina through the optic tract in mouse brain at embryonic day (E) 15-17, and these behaviors were matched with different growth cone forms. Patterns of behavior were then analyzed in the different locales from the retina through the optic tract. Throughout the pathway, episodes of advance were punctuated by pauses in extension. Irrespective of locale, elongated streamlined growth cones mediated advance and complex forms developed during pauses. The rate of advance and the duration of pauses were surprisingly similar in different parts of the pathway. In contrast, the duration of periods of advance was more brief in the chiasm compared to those in the optic nerve and tract. Consequently, in the chiasm, growth cones spent relatively more time pausing and less time advancing than in the optic nerve or tract. Thus, because growth cone form is behavior-specific and certain behaviors predominate in particular loci, growth cone form appears to be position-specific in static preparations, due to the fraction of time spent in a given state in different locales.

Animals↗
PubMed1997

Glia, neurons, and axon pathfinding during optic chiasm development.

The importance of vision in the behavior of animals, from invertebrates to primates, has led to a good deal of interest in how projection neurons in the retina make specific connections with targets in the brain. Recent research has focused on the cellular interactions occurring between retinal ganglion cell (RGC) axons and specific glial and neuronal populations in the embryonic brain during formation of the mouse optic chiasm. These interactions appear to be involved both in determining the position of the optic chiasm on the ventral diencephalon (presumptive hypothalamus) and in ipsilateral and contralateral RGC axon pathfinding, development events fundamental to binocular vision in the adult animal.

Animals↗
PubMed1997

Family support decreases influence of deviant peers on Hispanic adolescents' substance use.

Investigated the interplay of family support and peer modeling on adolescent alcohol, tobacco, and marijuana use and gang involvement within an ecosystemic model. The predominantly Hispanic sample of 236 eighth-grade students attended a public middle school in a high-density, impoverished Miami neighborhood, characterized by high rates of criminal activity, substance abuse, and other stressors, placing the adolescents at risk for negative developmental outcomes. The participants reported the level of perceived social support they received from family members and rates of drug use and gang, involvement for themselves and for peers. The results showed that family social support reduced the influence of deviant peers on some of the problem behaviors reported by these adolescents, specifically tobacco and marijuana use. Deviant peer modeling was strongly associated with levels of adolescent problem behavior for tobacco, alcohol and marijuana use and gang involvement.

Adolescent↗
PubMed1997

Early predictors of attachment in infants with cleft lip and/or palate.

Previous studies have found that children with cleft lip and palate (CLP) and isolated cleft palate (CP) have elevated risk for a variety of psychosocial problems, but the origins of such problems are unclear. We expected that early medical and other stressors during infancy--including feeding problems and facial disfigurement--would have adverse effects on the infant, his or her caregivers, and the family environment, leading to a higher than expected rate of insecure attachments among infants with clefts. Twelve-month attachment classifications of CLP, CP, and comparison group infants were examined. No significant group differences in attachment status were found. When 3-month infant, maternal, and social/family characteristics were examined as potential predictors of insecure attachment, predictors interacted with diagnostic status. For the cleft group, infant and maternal characteristics, but not family characteristics, significantly predicted insecure attachment. For the comparison group, maternal and family characteristics, but not factors associated with the infant, were predictive. Infants with clefts, despite their special needs and caregiving requirements, seem not to have elevated risk for insecure attachments at the end of their first year. Contrary to social-psychological formulations, the facial appearance of infants with CLP had no adverse effect on the quality of their maternal attachment.

Case-Control Studies↗
PubMed1997

Axon-target interactions in the developing cerebellum.

After entering target regions, afferent growth cones grow among putative target cells, stop extending upon meeting target cells, and transit into a synaptic ending. During these events, signals are transmitted to and from target cells to stimulate programs of differentiation. Here we describe three approaches to unraveling mechanisms of these phases of synaptogenesis. First, dye-labeling in the intact cerebellum has revealed the orchestration of afferent ingrowth and contacts with target cells. Second, an in vitro model based on purified granule neurons has shed light on the role of target cells in the arrest of afferent extension. Third, coculture of purified granule neurons (parallel fiber afferents) with purified Purkinje cells has demonstrated facets of afferent regulation of target cell differentiation. These analyses have suggested molecular mechanisms that mediate maturation of afferents and their targets.

Afferent Pathways↗
PubMed1996

Eph family receptors and their ligands distribute in opposing gradients in the developing mouse retina.

The Eph family of receptor tyrosine kinases and their ligands can be divided into two specificity subclasses: the Eck-related receptors and their GPI-anchored ligands, and the Elk-related receptors and their transmembrane ligands. Previous reports demonstrated that Eck- and Elk-related receptors in the retina distribute in high temporal-low nasal and high ventral-low dorsal gradients, respectively. While others have focused on complementary ligand gradients in the retinal axon target, the tectum, we report that ligands from each subclass also distribute in gradients opposing those of their corresponding receptors within the retina itself. Moreover, ligand gradients in the retina precede ganglion cell genesis. These results support an intraretinal role for Eph family members in addition to their previously proposed role in the development of retinotectal topography. The distinct distributions of Eph family members suggest that each subclass specifies positional information along independent retinal axes.

Animals↗
PubMed1996

Neuron death in the substantia nigra of weaver mouse occurs late in development and is not apoptotic.

Weaver is a spontaneous mutation in mice characterized by the postnatal loss of external granule cells in the cerebellum and dopaminergic neurons of the midbrain, especially in the substantia nigra. We have shown previously that natural cell death with the morphology of apoptosis occurs in the substantia nigra of normal rodents during postnatal development. We therefore sought to determine whether the loss of dopaminergic neurons in homozygous weaver mice occurs during the period of natural cell death in the substantia nigra and whether it has the morphology of apoptosis. We have found, using a silver stain technique, that although apoptotic cell death does occur early postnatally in homozygous weaver substantia nigra, it also does so with equal magnitude in wild-type and heterozygous weaver littermates. Unique to homozygous weavers is the occurrence of degenerating neurons in the nigra that are not apoptotic. These degenerating neurons are observed at postnatal day 7, and they are most abundant on postnatal days 24-25. The nonapoptotic nature of this cell death is confirmed by negative in situ end labeling of nuclear DNA fragmentation and by ultrastructural analysis. Ultrastructural studies reveal irregular chromatin aggregates in the nucleus, as well as marked cytoplasmic changes, including the formation of vacuoles and distinctive stacks of dilated cisternae of endoplasmic reticulum. We interpret these changes as indicative of either a variant morphology of programmed cell death or a pathological degenerative process mediated by an as yet unknown mechanism related to the recently described mutation in the GIRK2 potassium channel.

Aging↗
PubMed1996

Arrest of afferent axon extension by target neurons in vitro is regulated by the NMDA receptor.

Cerebellar granule neurons in vitro specifically arrest the extension of their appropriate presynaptic axons, mossy fibers. This "stop-growing signal" may be an essential step in the formation and specificity of synapses. Here, we have tested whether ionotropic glutamate receptors are involved in the stop-growing signal. When explants of basilar pontine nuclei, a mossy fiber source, were cultured on granule neurons, most pontine neurites terminated <200 microm from their explant of origin, a criterion for the stop-growing signal. In contrast, treatment with the NMDA antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) greatly increased the number of pontine neurites extending beyond 300 microm, whereas treatment with NMDA reduced the number of pontine neurites extending beyond 200 microm. A non-NMDA agonist (AMPA) and antagonist (6-cyano-7-nitroquinoxaline-2,3-dione) did not alter pontine neurite lengths. None of these agents affected neurite outgrowth from pontine explants in the absence of granule neurons, nor did any agent affect the survival of granule neurons. These results indicate that NMDA and D-AP5 specifically perturb an interaction between axons and target cells necessary for the stop-growing signal, and that NMDA receptors are critical for the development of a major cerebellar afferent system. These findings also suggest that NMDA-sensitive refinement of axon arbors during later development may involve the direct regulation of axon extension by target neurons.

Afferent Pathways↗
PubMed1996

Association of beta 1 integrin with phosphotyrosine in growth cone filopodia.

Filopodia of growth cones are key elements in the transduction of extracellular cues that guide axon growth during development. How they are specialized to carry out this role is poorly understood. We previously had found tyrosine phosphorylated protein to be heavily concentrated at the tips of many filopodia of Aplysia growth cones in certain culturing conditions, suggesting that tyrosine phosphorylation might be involved in filopodial specialization. Immunocytochemistry was used to analyze the protein composition of the tip aggregates to determine whether there was an association of the tip phosphorylation with any important extracellular cue. beta 1 integrin, a subunit of the receptor for laminin-type neurite growth promoters, coconcentrated with phosphotyrosine at filopodial tips of both Aplysia and mouse growth cones. Several observations indicated that the association of beta 1 integrin with phosphotyrosine is close. beta 1 integrin and phosphotyrosine are known to colocalize at focal contacts, sites of adhesion of cells to the extracellular matrix, but the composition and behavior of the tip aggregates mark them as distinct structures. Also found in the tip aggregates was a member of the ezrin-radixin-moesin family of proteins, which are thought to link membrane proteins to submembranous bundles of actin filaments. Use of an inhibitor of protein-tyrosine kinases to deplete tip phosphotyrosine also caused disappearance of beta 1 integrin from the tip, suggesting a role for tyrosine phosphorylation in facilitating interaction of growth cones with certain environmental cues by fostering the aggregation of receptors in filopodia.

Animals↗
PubMed1996

alpha-Internexin is the only neuronal intermediate filament expressed in developing cerebellar granule neurons.

We have used immunocytochemistry and in situ hybridization to examine the distribution of neuronal intermediate filament proteins and their mRNAs in the developing mouse cerebellum. First, we demonstrate that alpha-internexin is abundantly expressed in the developing cerebellum and is the only neuronal intermediate filament protein expressed in developing, including migrating, granule neurons. Second, in granule neuron reaggregates in vitro, alpha-internexin is the only neuronal intermediate filament protein highly expressed in the processes of the cultured granule neurons. This in vitro observation is consistent with results from immunocytochemistry and in situ hybridization studies of developing granule neurons in vivo, which suggest that alpha-internexin is the major neuronal intermediate filament protein in developing granule neurons. Finally, the neurofilament triplet proteins are expressed later, and coexist with alpha-internexin in other cells, including Purkinje cells and interneurons in the mature mouse cerebellum. These changes in neuronal intermediate filament composition may regulate neuronal maturation and axonal stability in cerebellar development. Furthermore, alpha-internexin may play a key role in neurite outgrowth and the establishment of neuronal cytoarchitecture.

Age Factors↗
PubMed1996

Family, peer, and neighborhood influences on academic achievement among African-American adolescents: one-year prospective effects.

Using a 1-year prospective design, this study examined the influence of family status variables (family income, parental education, family structure), parenting variables (maternal support and restrictive control), peer support, and neighborhood risk on the school performance of 120 African American junior high school students. In addition to main effects of these variables, neighborhood risk was examined as a moderator of the effects of parenting and peer support. Family status variables were not predictive of adolescent school performance as indexed by self-reported grade point average. Maternal support at Time 1 was prospectively related to adolescent grades at Time 2. Neighborhood risk was related to lower grades, while peer support predicted better grades in the prospective analyses. Neighborhood risk also moderated the effects of maternal restrictive control and peer support on adolescent grades in prospective analyses. These findings highlight the importance of an ecological approach to the problem of academic underachievement within the African American Community.

Achievement↗
PubMed1996

Chemosuppression of retinal axon growth by the mouse optic chiasm.

To determine whether diffusible guidance cues direct retinal axon growth and divergence at the optic chiasm, we cocultured mouse retinal and chiasm explants in collagen gels. The chiasm reduced retinal neurite lengths and numbers, but did not affect commissural or pontine neurite growth. This reduction in growth was equal for all retinal quadrants and occurred without reorienting the direction of neurite extension. The floor plate, another midline guidance locus, also suppressed retinal neurite outgrowth, whereas cortex or cerebellum explants did not. Growth suppression was not mediated by netrin-1, which instead enhanced retinal neurite extension. We propose that chemosuppression may be a general guidance mechanism that acts in intermediate targets to prime growth cones to perceive other, more specific cues.

Animals↗
PubMed1996

Retinal axon divergence in the optic chiasm: midline cells are unaffected by the albino mutation.

The visual pathway in albino animals is abnormal in that there is a smaller number of ipsilaterally projecting retinal ganglion cells. There are two possible sites of gene action that could result in such a defect. The first site is the retina where the amount of pigmentation in the retinal pigment epithelium is correlated with the degree of ipsilateral innervation (La Vail et al. (1978) J. Comp. Neurol. 182, 399-422). The second site is the optic chiasm, the site of retinal axon divergence. We investigated these two possibilities through a combination of in vivo and in vitro techniques. Our results demonstrate that the growth patterns of retinal axons and the cellular composition of the optic chiasm in albino mice are similar to those of normally pigmented mice, consistent with the albino mutation exerting its effects in the retina, and not on the cells from the chiasmatic midline. We directly tested whether the albino mutation affects the chiasm by studying 'chimeric' cultures of retinal explants and chiasm cells isolated from pigmented and albino mice. Crossed and uncrossed axons from pigmented or albino retinal explants display the same amount of differential growth when grown on either pigmented or albino chiasm cells, demonstrating that the albino mutation does not disrupt the signals for retinal axon divergence associated with the albino optic chiasm. Furthermore, in vitro, a greater proportion of albino retinal ganglion cells from ventrotemporal retina, origin of uncrossed axons, behave like crossed cells, suggesting that the albino mutation acts by respecifying the numbers of retinal ganglion cells that cross the chiasmatic midline.

Albinism↗
PubMed1996

Interobserver agreement in the assessment of parental behavior and parent-adolescent conflict: African American mothers, daughters, and independent observers.

Agreement between 57 African American mothers and their early adolescent daughters on measures of maternal support, maternal restrictive control, and parent-adolescent conflict were examined. To assess the relative validity of these reports, the study then evaluated them against the ratings of independent observers. Additionally, mother and daughter reports were combined to examine validity coefficients based on aggregate scores of each construct. All analyses were based on 2 sets of objective criterion ratings: ratings provided by coders of similar ethnic background (African American) and coders who were ethnically dissimilar (non-African American) to the families they rated. Overall, adolescents provided ratings that were more valid than those of their mothers when evaluated against both sets of independent ratings. Adolescent ratings of maternal control and parent-adolescent conflict converged at significantly higher levels than the ratings provided by their mothers. Maternal and adolescent reports of maternal support converged with objective criteria at statistically comparable levels. Validity coefficients for adolescent reports were also higher than those based on aggregate mother-daughter scores. Secondary analyses further revealed that African American coders rated mothers as less controlling and rated the dyadic interactions as less conflictual, and that their ratings were more consistent with the perceptions of the African American mothers and adolescents than were those provided by non-African American coders.

Adolescent↗
PubMed1996

Neither too sweet nor too sour: problem peers, maternal control, and problem behavior in African American adolescents.

This study examined whether maternal control protects African American adolescents from the negative influence of problem peers. Two forms of control were examined, behavioral control and psychological control. It was hypothesized that there would be a curvilinear relation between control and adolescent problem behavior, with the strength of the relationship and the amount of control optimal for adolescent development varying by the level of peer problem behavior. In general, data supported this model, particularly in regard to behavioral control, where the predicted curvilinear interaction occurred even after controlling for initial levels of problem behavior. The predicted curvilinear interaction between psychological control and peer problem behavior was statistically significant if initial levels of problem behavior were not controlled for but was not significant after controlling for initial problem behavior. These findings suggest that high-quality parenting can play a modest but critical role in the face of environmental adversity.

Adolescent↗