Juli Wade

Michigan State University, Ист-Лансинг, Michigan, United States

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Publications (117)433 Total impact

  • Halie N Kerver · Juli Wade
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    ABSTRACT: Green anoles are seasonally breeding lizards in which male sexual behavior is primarily regulated by an annual increase in testosterone. This hormone activates stereotyped behaviors, as well as morphological and biochemical changes in the brain, with greater effect in the breeding season than in the non-breeding season. This study is the first description of CREB binding protein (CBP) in the reptilian brain, and investigates the possibility that changes in CBP, an androgen receptor coactivator, may facilitate differences in responsiveness to testosterone across seasons. A portion of this gene was cloned for the green anole, and in situ hybridization was performed to examine the expression of CBP in the brains of gonadally intact male and female green anoles across breeding states. Additionally, hormonal regulation of CBP was evaluated across sex and season in animals that were gonadectomized and treated with testosterone or a control. Similar to other vertebrates, CBP was expressed at relatively high levels in steroid-sensitive brain regions. In the anole ventromedial amygdala, CBP mRNA levels were nearly twice as high in gonadally intact females compared to males. In contrast, CBP expression did not differ across seasons or hormone manipulation in this brain region. No significant effects were detected in the preoptic area or ventromedial hypothalamus. This pattern suggests that CBP might influence female-biased functions controlled by the ventromedial amygdala, but is not consistent with a role in mediating seasonal differences in responsiveness to testosterone in these areas associated with reproductive function.
    No preview · Article · Sep 2015 · General and Comparative Endocrinology
  • Yu Ping Tang · Juli Wade
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    ABSTRACT: The neural song circuit is enhanced in male compared to female zebra finches due to differential rates of incorporation and survival of cells between the sexes. Two double-label immunohistochemical experiments were conducted to increase the understanding of relationships between newly generated cells (marked with bromodeoxyuridine, BrdU) and those expressing brain derived neurotrophic factor (BDNF) and vimentin, a marker for radial glia. The song systems of males and females were investigated at post-hatching day 25 during a heightened period of sexual differentiation (following BrdU injections on days 6-10) and in adulthood (following a parallel injection paradigm). In both HVC (proper name) and the robust nucleus of the archopallium (RA), about half of the BrdU-positive cells expressed BDNF across sexes and ages. Less than 10% of the BDNF-positive cells expressed BrdU, but this percentage was greater in juveniles than adults. Across both brain regions, more BDNF-positive cells were detected in males compared to females. In RA, the number of these cells was also greater in juveniles than adults. In HVC, the average cross-sectional area covered by the vimentin labeling was greater in males than females and in juveniles compared to adults. In RA, more vimentin was detected in juveniles than adults, and within adults it was greater in females. In juveniles only, BrdU-positive cells appeared in contact with vimentin labeled fibers in HVC, RA and Area X. Collectively, the results are consistent with roles of BDNF and vimentin-labeled cells influencing sexual differentiated plasticity of the song circuit. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · The Journal of Comparative Neurology
  • Halie N. Kerver · Juli Wade
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    ABSTRACT: Green anole lizards are seasonal breeders, with male sexual behaviour primarily regulated by an annual increase in testosterone (T). Morphological, biochemical and behavioural changes associated with reproduction are activated by T, generally with greater effect in the breeding season (BS) than in the non-breeding season (NBS). This paper investigates the possibility that differences in a steroid receptor coactivator may regulate this seasonal difference in responsiveness to T. In situ hybridisation was used to examine the expression of steroid receptor coactivator-1 (SRC-1) in the brains of gonadally intact male and female green anoles across breeding states. A second experiment examined gonadectomised animals with and without T-treatment. Gonadally intact males had more SRC-1 expressing cells in the preoptic area and larger volumes of this region as defined by these cells than females. Main effects of both sex and season (males>females and BS>NBS) were present in cell number and volume of the ventromedial hypothalamus. An interaction between sex and season suggested that high expression in BS males was driving these effects. In hormone-manipulated animals, T-treatment increased both the number of SRC-1 expressing cells in and volumes of the preoptic area and amygdala. These results suggest that T selectively regulates SRC-1, and that this coactivator may play a role in facilitating reproductive behaviours across both sexes. However, changes in SRC-1 expression are not likely responsible for the seasonal change in responsiveness to T.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Neuroendocrinology
  • Halie N Kerver · Juli Wade
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    ABSTRACT: Sexual behavior in male green anole lizards is regulated by a seasonal increase in testosterone (T). However, T is much more effective at activating behavioral, morphological and biochemical changes related to reproduction in the breeding season (BS; spring) compared to nonbreeding season (NBS; fall). An increase in androgen receptor (AR) during the BS is one potential mechanism for this differential responsiveness. AR expression has not been investigated in specific brain regions across seasons in anoles. The present studies were designed to determine relative AR expression in areas important for male (preoptic area, ventromedial amygdala) and female (ventromedial hypothalamus) sexual behavior, as well as whether T upregulates AR in the anole brain. In situ hybridization and Western blot analyses were performed in unmanipulated animals across sex and season, as well as in gonadectomized animals with and without T treatment. Among hormone-manipulated animals, more cells expressing AR mRNA were detected in females than males in the amygdala. T treatment increased the volume of the ventromedial hypothalamus of gonadectomized animals in the BS, but not the NBS. AR protein in dissections of the hypothalamus and preoptic area was increased in males compared to females specifically in the BS. Additionally, among females, it was increased in the NBS compared to the BS. Collectively, these results indicate that differences in central AR expression probably do not facilitate a seasonal responsiveness to T. However, they are consistent with a role for AR in regulating some differences between sexes in the display of reproductive behaviors. © 2014 S. Karger AG, Basel.
    No preview · Article · Nov 2014 · Brain Behavior and Evolution
  • Yu Ping Tang · Juli Wade
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    ABSTRACT: This study investigated relationships among disruption of normal vocal learning, brain derived neurotrophic faction (BDNF), and the morphology of song nuclei in juvenile male zebra finches. The tracheosyringeal nerves were bilaterally transected at post-hatching day 20-25, so that the animals could not properly develop species-typical vocalizations. BDNF protein and the projection from HVC to the robust nucleus of the arcopallium (RA) were quantified during the sensorimotor integration phase of song development. The manipulation decreased the number of BDNF cells in HVC and RA, the volume of these areas defined by BDNF labeling, and the projection from HVC to RA. BDNF was not affected in Area X or the lateral magnocellular nucleus of the anterior nidopallium (LMAN). Thus, inhibition of a bird's ability to practice and/or to hear its own typically developing song during development specifically diminishes BDNF expression in cortical motor regions required for song production.
    No preview · Article · Sep 2014 · Neuroscience Letters
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    ABSTRACT: Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Yu Ping Tang · Juli Wade
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    ABSTRACT: The zebra finch song system provides an excellent model to study the mechanisms underlying the development of sex difference in brain structure and function. Only male zebra finches sing and the brain nuclei controlling song learning and production are considerably larger than in females. Sexual differentiation may in part be regulated by estrogen, but other molecules including neurotrophic factors likely also affect masculinization. Brain derived neurotrophic factor (BDNF) plays crucial roles in numerous aspects of vertebrate brain development and function, including neurogenesis, cell survival, growth of axonal projections, synaptogenesis and processes linked to learning and memory. The current study investigated expression of BDNF protein in juvenile males and females at four ages, as well as in adults, to begin to evaluate the potential roles of endogenous BDNF in particular stages of structural and functional development of the song system. In both HVC and the robust nucleus of the arcopallium (RA), males had more BDNF+ cells than females. The number of immunopositive cells increased in males and decreased in females as they matured, in a pattern generally consistent with a role for BDNF in sensorimotor integration of song learning. In addition, in HVC (but not RA) the ratio of mature BDNF (mBDNF) compared to its precursor proBDNF was greater in adult males than those at post-hatching day 25, indicating a region-specific shift in the relative availability of the two forms. Collectively, the data suggest that changes in BDNF protein expression across development may be associated with song system maturation, particularly during the sensorimotor integration of masculine vocalizations.
    No preview · Article · Aug 2013 · Neuroscience
  • Halie N Kerver · Juli Wade
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    ABSTRACT: Green anoles are seasonally breeding lizards, with an annual rise in testosterone (T) being the primary activator of male sexual behaviors. Responsiveness to T is decreased in the non-breeding season (NBS) compared to breeding season (BS) on a variety of levels, including displays of reproductive behavior and the morphology and biochemistry of associated tissues. To evaluate the possibility that seasonal changes in responsiveness to T are regulated by androgen receptors (AR) and/or two of its coactivators, CREB binding protein (CBP) and steroid receptor coactivator-1 (SRC-1), we tested whether they differ in expression across season in brains of both sexes and in peripheral copulatory tissues of males (hemipenis and retractor penis magnus muscle). AR mRNA was increased in the brains of males compared to females and in copulatory muscle in the BS compared to NBS. In the hemipenis, transcriptional activity appeared generally diminished in the NBS. T-treatment increased AR mRNA in the copulatory muscle and AR protein in the hemipenis, the latter to a greater extent in the BS than the NBS. T also decreased SRC-1 protein in hemipenis. Interpretations are complicated, in part because levels of mRNA and protein expression were not correlated and multiple sizes of the AR and CBP proteins were detected, with some tissue specificity. However, the results are consistent with the idea that differences in receptor and coactivator expression at central and peripheral levels may play roles in regulating sex and seasonal differences in the motivation or physical ability to engage in sexual behavior.
    No preview · Article · Jul 2013 · General and Comparative Endocrinology
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    Gregory F Ball · Juli Wade
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    ABSTRACT: This article is part of a Special Issue "Puberty and Adolescence". Studies of birds and reptiles have provided many basic insights into the neuroendocrine control of reproductive processes. This research has elucidated mechanisms regulating both early development, including sexual differentiation, and adult neuroendocrine function and behavior. However, phenomena associated with the transition into sexual maturation (puberty) have not been a focus of investigators working on species in these taxonomic classes. Research is complicated in birds and reptiles by a variety of factors, including what can be extended times to maturation, the need to reach particular body size regardless of age, and environmental conditions that can support or inhibit endocrine responses. However, careful selection of model systems, particularly those with available genetic tools, will lead to important comparative studies that can elucidate both generalizability and diversity of mechanisms regulating the onset of reproductive maturity.
    Full-text · Article · Jul 2013 · Hormones and Behavior
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    Linda M Qi · Juli Wade
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    ABSTRACT: Sex differences in brain and behavior exist across vertebrates, but the molecular factors regulating their development are largely unknown. Songbirds exhibit substantial sexual dimorphisms. In zebra finches, only males sing, and the brain areas regulating song learning and production are much larger in males. Recent data suggest that sex chromosome genes (males ZZ; females ZW) may play roles in sexual differentiation. The present studies tested the hypothesis that a Z-gene, tubulin specific chaperone protein A (TBCA), contributes to sexual differentiation of the song system. This taxonomically conserved gene is integral to microtubule synthesis, and within the song system, its mRNA is specifically increased in males compared to females in the lateral magnocellular nucleus of the anterior nidopallium (LMAN), a region critical for song learning and plasticity. Using in situ hybridization, Western blot analysis, and immunohistochemistry, we observed effects of both age and sex on TBCA mRNA and protein expression. The transcript is increased in males compared to females at three juvenile ages, but not in adults. TBCA protein, both the number of immunoreactive cells and relative concentration in LMAN, is diminished in adults compared to juveniles. The latter was also increased in males compared to females at post-hatching day 25. With double-label immunofluorescence and retrograde tract tracing, we also document that the majority of TBCA+ cells in LMAN are neurons, and that they include RA-projecting cells. These results indicate that TBCA is both temporally and spatially primed to facilitate the development of a sexually dimorphic neural pathway critical for song.
    Full-text · Article · May 2013 · Neuroscience
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    ABSTRACT: The neural song system in zebra finches is highly sexually dimorphic; only males sing and the brain regions controlling song are far larger in males than females. Estradiol (E2) administered during development can partially masculinize both structure and function. However, additional mechanisms, including those through which E2 may act, remain unclear. Male and female zebra finches were treated with E2 or control vehicle from post-hatching days 3 through 25, at which time norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured in individual nuclei of the song system. Main effects of sex were not detected. However, E2 increased NE in the robust nucleus of the arcopallium (RA). In HVC (proper name), the hormone decreased 5-HT across the two sexes and increased DA in females only. These effects suggest that, while baseline levels of these neurotransmitters may not contribute to sexually dimorphic development of the song system, they could play specific roles in functions common to both sexes and/or in modification of the song system by exogenous E2.
    Full-text · Article · Apr 2013 · Brain research
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    ABSTRACT: During development, male zebra finches learn a song that they eventually use in courtship and defense of nest sites. Norepinephrine (NE) is important for learning and memory in vertebrates, and this neuromodulator and its receptors are present throughout the brain regions that control song learning and production. The present study used the neurotoxin N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) to reduce brain levels of NE in juvenile males. This manipulation inhibited the development of quality songs, with some birds producing syllables that were unusually long and/or contained frequencies that were predominantly higher than normal. These results suggest that NE is important for the acquisition of typical song.
    Full-text · Article · Nov 2012 · Brain research bulletin
  • Rachel E. Cohen · Juli Wade
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    ABSTRACT: In the brain, testosterone (T) can be metabolized into estradiol via the action of the aromatase enzyme, and into 5α-dihydrotestosterone via the action of the 5α-reductase (5αR) enzyme. This chapter discusses aromatase and 5αR in reptiles, with a focus on green anole lizards. The chapter examines the role of aromatase and 5αR on reproductive behavior in this species. Next the chapter examines the whole brain activity of aromatase and 5αR, as well as the mRNA distribution of these enzymes in three brain areas critical for reproduction: the preoptic area, amygdala, and ventromedial hypothalamus. Finally the chapter discusses the expression of these enzymes in juvenile anoles. Overall, the experiments presented here highlight the importance of comparative work and lay groundwork for future research that will ascertain the role of these enzymes in anoles and the extent of their regulation by T.
    No preview · Chapter · Oct 2012
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    ABSTRACT: Songbirds provide rich natural models for studying the relationships between brain anatomy, behavior, environmental signals, and gene expression. Under the Songbird Neurogenomics Initiative, investigators from 11 laboratories collected brain samples from six species of songbird under a range of experimental conditions, and 488 of these samples were analyzed systematically for gene expression by microarray. ANOVA was used to test 32 planned contrasts in the data, revealing the relative impact of different factors. The brain region from which tissue was taken had the greatest influence on gene expression profile, affecting the majority of signals measured by 18,848 cDNA spots on the microarray. Social and environmental manipulations had a highly variable impact, interpreted here as a manifestation of paradoxical “constitutive plasticity” (fewer inducible genes) during periods of enhanced behavioral responsiveness. Several specific genes were identified that may be important in the evolution of linkages between environmental signals and behavior. The data were also analyzed using weighted gene coexpression network analysis, followed by gene ontology analysis. This revealed modules of coexpressed genes that are also enriched for specific functional annotations, such as “ribosome” (expressed more highly in juvenile brain) and “dopamine metabolic process” (expressed more highly in striatal song control nucleus area X). These results underscore the complexity of influences on neural gene expression and provide a resource for studying how these influences are integrated during natural experience.
    Full-text · Article · Oct 2012 · Proceedings of the National Academy of Sciences
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    Yu Ping Tang · Juli Wade
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    ABSTRACT: Mature brain derived neurotrophic factor (BDNF) plays critical roles in development of brain structure and function, including neurogenesis, axon growth, cell survival and processes associated with learning. Expression of this peptide is regulated by estradiol (E2). The zebra finch song system is sexually dimorphic - only males sing and the brain regions controlling song are larger and have more cells in males compared to females. Masculinization of this system is partially mediated by E2, and earlier work suggests that BDNF with its high affinity receptor TrkB may also influence this development. The present study evaluated expression of multiple forms of both BDNF and TrkB in the developing song system in juvenile males and females treated with E2 or a vehicle control. Using immunohistochemistry and Western blot analysis, BDNF was detected across the song nuclei of 25-day-old birds. Westerns allowed the pro- and mature forms of BDNF to be individually identified, and proBDNF to be quantified. Several statistically significant effects of sex existed in both the estimated total number of BDNF+ cells and relative concentration of proBDNF, varying across the regions and methodologies. E2 modulated BDNF expression, although the specific nature of the regulation depended on brain region, sex and the technique used. Similarly, TrkB (both truncated and full-length isoforms) was detected by Western blot in the song system of juveniles of both sexes, and expression was regulated by E2. In the context of earlier research on these molecules in the developing song system, this work provides a critical step in describing specific forms of BDNF and TrkB, and how they can be mediated by sex and E2. As individual isoforms of each can have opposing effects on mechanisms, such as cell survival, it will now be important to investigate in depth their specific functions in song system maturation.
    Full-text · Article · Aug 2012 · PLoS ONE
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    R E Cohen · J Wade
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    ABSTRACT: Neural steroids, as well as the enzymes that produce these hormones, are important for sexual differentiation of the brain during development. Aromatase converts testosterone into oestradiol. 5α-reductase converts testosterone to 5α-dihydrotestosterone and occurs in two isozymes: type 1 (5αR1) and type 2 (5αR2). Each of these enzymes is present in the developing brain in many species, although no work has been carried out examining the expression of all three enzymes in non-avian reptiles with genetic sex determination. In the present study, we evaluated mRNA expression of neural aromatase, 5αR1 and 5αR2, on the day of hatching and at day 50 in one such lizard, the green anole. We describe the distribution of these enzymes throughout the brain and the quantification of mRNA expression in three regions that control adult sexual behaviours: the preoptic area (POA) and ventromedial amygdala (AMY), which are involved in male displays, as well as the ventromedial hypothalamus, which regulates female receptivity. Younger animals had a greater number (POA) and density (AMY) of 5αR1 mRNA expressing cells. We detected no effects of sex or age on aromatase or 5αR2. In comparison with data from adults, the present results support the idea that the green anole forebrain has not completely differentiated by 50 days after hatching and that 5αR1 may play a role in the early development of regions important for masculine function.
    Preview · Article · Apr 2012 · Journal of Neuroendocrinology
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    Rachel E Cohen · Juli Wade
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    ABSTRACT: Aromatase and 5α-reductase (5αR) catalyze the synthesis of testosterone (T) metabolites: estradiol and 5α-dihydrotestosterone, respectively. These enzymes are important in controlling sexual behaviors in male and female vertebrates. To investigate factors contributing to their regulation in reptiles, male and female green anole lizards were gonadectomized during the breeding and non-breeding seasons and treated with a T-filled or blank capsule. In situ hybridization was used to examine main effects of and interactions among sex, season, and T on expression of aromatase and one isozyme of 5αR (5αR2) in three brain regions that control reproductive behaviors: the preoptic area, ventromedial nucleus of the amygdala and ventromedial hypothalamus (VMH). Patterns of mRNA generally paralleled previous evaluations of intact animals. Although no main effects of T were detected, interactions were present in the VMH. Specifically, the density of 5αR2 expressing cells was greater in T-treated than control females in this region, regardless of season. Among breeding males, blank-treated males had a denser population of 5αR2 positive cells than T-treated males. Overall, T appears to have less of a role in the regulation of these enzymes than in other vertebrate groups, which is consistent with the primary role of T (rather than its metabolites) in regulation of reproductive behaviors in lizards. However, further investigation of protein and enzyme activity levels are needed before specific conclusions can be drawn.
    Full-text · Article · Feb 2012 · General and Comparative Endocrinology
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    Linda M Qi · Margaret Mohr · Juli Wade
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    ABSTRACT: Recent evidence suggests that sexual dimorphisms in the zebra finch song system and behavior arise due to factors intrinsic to the brain, rather than being solely organized by circulating steroid hormones. The present study examined expression of 10 sex chromosome genes in the song system of 25-day-old zebra finches in an attempt to further elucidate these factors. Increased expression in males was confirmed for nine of the genes by real-time qPCR using cDNA from individual whole telecephalons. In situ hybridization at the same age revealed specific, male-enhanced mRNA for three of the nine genes in one or more song control nuclei. These genes encode tubulin-specific chaperone A, mitochondrial ribosomal protein S27, and a DNA repair protein XPACCH. Based on what is currently known about these proteins' functions and their localization to particular components of the song circuit, we hypothesize that they each may be involved in specific aspects of masculinization.
    Full-text · Article · Feb 2012 · Developmental Neurobiology
  • Michele A. Johnson · Juli Wade
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    ABSTRACT: Reptiles provide ideal opportunities for addressing many questions regarding the neuroendocrinology of reproduction. This chapter describes the use of comparisons among and within reptilian species that allow detailed investigations of the relationships between neuroendocrine mechanisms and reproductive behaviors. This chapter primarily focuses on the features associated with displays of sexual behavior, drawing mostly from research on the species that have been most extensively studied. It considers behavioral displays in their ecological contexts, associated seasonal and hormonal changes, the muscles and portions of the nervous system critical for production of the behaviors, and the development and plasticity of reproductive traits. It also attempts to integrate across the levels and discuss relationships among morphology, behavior, and the endocrine and other mechanisms regulating these traits. Territorial aggression and dominance (and the stress associated with these social behaviors) are also critical components of reproductive success that involve neuroendocrine mechanisms, including an important role for neurotransmitters.
    No preview · Article · Dec 2011
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    Juli Wade
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    ABSTRACT: Morphology parallels function on a variety of levels in reproductive circuits in anole lizards, as in many vertebrate groups. For example, across species within the anole genus the muscle fibers regulating extension of a throat fan used in courtship are larger in males than females. Endocrine factors controlling behavior and morphology have been studied in detail in one species, the green anole (Anolis carolinensis). This review briefly describes the results that have been obtained and highlights key areas for future investigation that will provide insights on mechanisms from a comparative perspective.
    Preview · Article · Dec 2011 · General and Comparative Endocrinology

Publication Stats

3k Citations
433.00 Total Impact Points

Institutions

  • 1997-2015
    • Michigan State University
      • • Department of Psychology
      • • Department of Zoology
      • • Department of Neuroscience
      Ист-Лансинг, Michigan, United States
  • 2005
    • Champalimaud Neuroscience Program
      Lisboa, Lisbon, Portugal
  • 1994-1995
    • University of California, Los Angeles
      • Department of Psychology
      Los Ángeles, California, United States
    • Laureate Institute for Brain Research
      Tulsa, Oklahoma, United States