Dale R Sengelaub

Indiana University Bloomington, Bloomington, Indiana, United States

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Publications (108)427.08 Total impact

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    ABSTRACT: After injury or insult to a motor system, gonadal steroids play a key role in regeneration and repair of motor function primarily through interactions with their intracellular receptors. This chapter highlights the protective and therapeutic effects that gonadal steroids have on neuronal functioning, ranging from motoneuron survival to enhancement of axonal and dendritic growth, as well as peripheral maintenance of bone and muscle. The systemic actions of gonadal steroids are truly multifaceted, modifying the entire synaptic response as well as targeting multiple tissues. We discuss the effects of gonadal steroids in both the central and the peripheral nervous systems ranging from their role in establishing important neuromuscular sex differences and their ability to protect against motoneuron death and disease, to triggering a regenerative response from both axons and dendrites, to enhancing bone growth and muscle mass after injury.
    Neural Regeneration, 12/2015: pages 129-150; , ISBN: 9780128017326
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    Nikki M Rendon · Lauren M Rudolph · Dale R Sengelaub · Gregory E Demas ·
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    ABSTRACT: Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.
    Proceedings of the Royal Society B: Biological Sciences 11/2015; 282(20152080). DOI:10.1098/rspb.2015.2080 · 5.05 Impact Factor
  • Rebecca Gregory · Hu Cheng · Heather A Rupp · Dale R. Sengelaub · Julia R Heiman ·
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    ABSTRACT: After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother-infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual desire was positively correlated with VTA activation to sexual images and with SES. Our findings show that postpartum decreases in sexual desire may in part be mediated by VTA activation, and oxytocin increased activation of the VTA but not NAc in response to sexual and infant stimuli. Oxytocin may contribute to the altered reproductive priorities in postpartum women by increasing VTA activation to salient infant stimuli. Copyright © 2014. Published by Elsevier Inc.
    Hormones and Behavior 01/2015; 69. DOI:10.1016/j.yhbeh.2014.12.009 · 4.63 Impact Factor
  • Rena M. Meadows · Dale R. Sengelaub · Kathryn J. Jones ·
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    ABSTRACT: Sensory and motor deficits resulting from peripheral nerve injury negatively impact quality of life and can require long-term rehabilitation and care. Despite the ability of nerves to robustly regenerate following peripheral nerve injury (PNI), functional recovery is often suboptimal. Surgery is required to treat patients in 50% of PNI cases, and there is no nonsurgical treatment strategy in clinical use today to treat PNI. Emerging evidence indicates that treatments affecting multiple targets and pathways have great potential. Here, we discuss data combining surgical repair with membrane fusion, electrical stimulation, and androgens to maintain appropriate channels for axons to regenerate back to their appropriate target and accelerate the regeneration process. Developing a therapy that impacts both axonal regeneration and functional recovery offers immediate translational opportunity in a clinical setting.
  • Nai-Kui Liu · James S Byers · Thomas Lam · Qing-Bo Lu · Dale R Sengelaub · Xiao-Ming Xu ·
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    ABSTRACT: Surviving motoneurons undergo dendritic atrophy after spinal cord injury (SCI), suggesting an important therapeutic target for neuroprotective strategies to improve recovery of function after SCI. Our previous studies showed that phospholipase A2 (PLA2) may play an important role in the pathogenesis of SCI. In the present study, we investigated whether blocking cPLA2 pharmacologically with arachidonyl trifluoromethyl ketone (ATK) or genetically using cPLA2 knockout (KO) mice attenuates motoneuron atrophy following SCI. C57BL/6 mice received either sham or contusive SCI at the T10 level. At 30 min after SCI, mice were treated with ATK or vehicle. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross-sectional area, and motor endplate size and density. ATK administration reduced percent lesion volume and increased percent volume of spared white matter compared to the vehicle-treated control animals. SCI with or without ATK treatment had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with ATK. Similarly, the vastus lateralis muscle weights of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were prevented by ATK treatment. No effects on fiber cross-sectional areas, motor endplate area or density were observed across treatment groups. Remarkably, genetically deleting cPLA2 in cPLA2 KO mice attenuated dendritic atrophy after SCI. These findings suggest that after SCI, cord tissue damage and regressive changes in motoneuron and muscle morphology can be reduced by inhibition of cPLA2, further supporting a role for cPLA2 as a neurotherapeutic target for SCI treatment.
    Journal of Neurotrauma 11/2014; DOI:10.1089/neu.2014.3690 · 3.71 Impact Factor
  • Nicholas J Thompson · Dale R Sengelaub · Arthur W English ·
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    ABSTRACT: Moderate exercise in the form of treadmill training and brief electrical nerve stimulation both enhance axon regeneration after peripheral nerve injury. Different regimens of exercise are required to enhance axon regeneration in male and female mice (Wood et al.: Dev Neurobiol 72 (2012) 688-698), and androgens are suspected to be involved. We treated mice with the androgen receptor blocker, flutamide, during either exercise or electrical stimulation, to evaluate the role of androgen receptor signaling in these activity-based methods of enhancing axon regeneration. The common fibular (CF) and tibial (TIB) nerves of thy-1-YFP-H mice, in which axons in peripheral nerves are marked by yellow fluorescent protein (YFP), were transected and repaired using CF and TIB nerve grafts harvested from non-fluorescent donor mice. Silastic capsules filled with flutamide were implanted subcutaneously to release the drug continuously. Exercised mice were treadmill trained 5 days/week for 2 weeks, starting on the third day post-transection. For electrical stimulation, the sciatic nerve was stimulated continuously for 1 h prior to nerve transection. After 2 weeks, lengths of YFP+ profiles of regenerating axons were measured from harvested nerves. Both exercise and electrical stimulation enhanced axon regeneration, but this enhancement was blocked completely by flutamide treatments. Signaling through androgen receptors is necessary for the enhancing effects of treadmill exercise or electrical stimulation on axon regeneration in cut peripheral nerves. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
    Developmental Neurobiology 05/2014; 74(5). DOI:10.1002/dneu.22147 · 3.37 Impact Factor
  • Douglas A. Lappi · Jack Feldman · Dale Sengelaub · Jill McGaughy ·
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    ABSTRACT: This chapter discusses the use of ribosome-inactivating protein (RIP) conjugates to understand the workings of the nervous systems. Different conjugates utilize different several different targeting agents, antibodies, peptide ligands, cytokines, or lectins, for elimination of specific cell types that express the target. This fits well with the history of neuroscientists who have lesioned a particular nervous system structure to determine its function from a loss or even gain of a behavioral process. We term the process Molecular Neurosurgery and here describe some of the ways researchers have used these materials in both research and therapeutic applications.
    Ribosome-inactivating Proteins, 04/2014: pages 253-269; , ISBN: 9781118125656
  • Lauren M Rudolph · Dale R Sengelaub ·
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    ABSTRACT: The spinal cord of rats contains the sexually dimorphic motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In males, SNB dendrites fail to grow after castration, but androgen or estrogen treatment supports dendritic growth in castrated males. Estrogenic support of SNB dendrite growth is mediated by estrogen receptors (ER) in the target muscle. ERα expression in cells lacking a basal lamina (referred to as "extra-muscle fiber cells") of the SNB target musculature coincides with the period of estrogen-dependent SNB dendrite growth. In the SNB target muscle, extra-muscle fiber ERα expression declines with age and is typically absent after postnatal (P) day 21 (P21). Given that estradiol downregulates ERα in skeletal muscle, we tested the hypothesis that depleting gonadal hormones would prevent the postnatal decline in ERα expression in the SNB target musculature. We castrated male rats at P7 and assessed ERα immunolabeling at P21; ERα expression was significantly greater in castrated males compared with normal animals. Because ERα expression in SNB target muscles mediates estrogen-dependent SNB dendrogenesis, we further hypothesized that the castration-induced increase in muscle ERα would heighten the estrogen sensitivity of SNB dendrites. Male rats were castrated at P7 and treated with estradiol from P21 to P28; estradiol treatment in castrates resulted in dendritic hypertrophy in SNB motoneurons compared with normal males. We conclude that early castration results in an increase in ERα expression in the SNB target muscle, and this upregulation of ERα supports estrogen sensitivity of SNB dendrites, allowing for hypermasculinization of SNB dendritic arbors. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
    Developmental Neurobiology 12/2013; 73(12). DOI:10.1002/dneu.22118 · 3.37 Impact Factor
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  • Tom Verhovshek · Dale R Sengelaub ·
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    ABSTRACT: We have previously demonstrated that brain-derived neurotrophic factor (BDNF) interacts with testosterone to regulate dendritic morphology of motoneurons in the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB). Additionally, in adult male rats testosterone regulates BDNF in SNB motoneurons and its target muscle, the bulbocavernosus (BC). Because BDNF is retrogradely transported from skeletal muscles to spinal motoneurons, we hypothesized that testosterone could regulate BDNF in SNB motoneurons by acting locally at the BC muscle. To test this hypothesis, we restricted androgen manipulation to the SNB target musculature. After castration, BDNF immunolabeling in SNB motoneurons was maintained at levels similar to those of gonadally intact males by delivering testosterone treatment directly to the BC muscle. When the same implant was placed interscapularly in castrated males it was ineffective in supporting BDNF immunolabeling in SNB motoneurons. Furthermore, BDNF immunolabeling in gonadally intact adult males given the androgen receptor blocker hydroxyflutamide delivered directly to the BC muscle was decreased compared to that of gonadally intact animals that had the same hydroxyflutamide implant placed interscapularly, or when compared to castrated animals that had testosterone implants at the muscle. These results demonstrate that the BC musculature is a critical site of action for the androgenic regulation of BDNF in SNB motoneurons and that it is both necessary and sufficient for this action. Furthermore, the local action of androgens at the BC muscle in regulating BDNF provides a possible mechanism underlying the interactive effects of testosterone and BDNF on motoneuron morphology. © 2013 Wiley Periodicals, Inc. Develop Neurobiol, 2013.
    Developmental Neurobiology 08/2013; 73(8). DOI:10.1002/dneu.22083 · 3.37 Impact Factor
  • Mollee R Farrell · Dale R Sengelaub · Cara L Wellman ·
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    ABSTRACT: There are sex differences in the rates of many stress-sensitive psychological disorders such as post traumatic stress disorder (PTSD). As medial prefrontal cortex and amygdala are implicated in many of these disorders, understanding differential stress effects in these regions may shed light on the mechanisms underlying sex-dependent expression of disorders like depression and anxiety. Prefrontal cortex and amygdala are key regions in the neural circuitry underlying fear conditioning and extinction, which thus has emerged as a useful model of stress influences on the neural circuitry underlying regulation of emotional behavior. This review outlines the current literature on sex differences and stress effects on dendritic morphology within medial prefrontal cortex and basolateral amygdala. Such structural differences and/or alterations can have important effects on fear conditioning and extinction, behaviors that are mediated by the basolateral amygdala and prefrontal cortex, respectively. Given the importance of extinction-based exposure therapy as a treatment for anxiety disorders such as PTSD, understanding the neural mechanisms by which stress differentially influences fear learning and extinction in males and females is an important goal for developing sex-appropriate interventions for stress-related disorders.
    Physiology & Behavior 04/2013; 122. DOI:10.1016/j.physbeh.2013.04.002 · 2.98 Impact Factor
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    Lauren M Rudolph · Dale R Sengelaub ·
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    ABSTRACT: The spinal cord of rats contains the sexually dimorphic, steroid-sensitive motoneurons of the spinal nucleus of the bulbocavernosus (SNB). In males, SNB dendrite growth is dependent on gonadal steroids: dendrite growth is inhibited after castration, but supported in androgen- or estrogen-treated castrated males. Furthermore, estrogenic support of SNB dendrite growth is mediated by estrogen action at the target musculature, inhibited by estrogen receptor (ER) blockade at the muscle and supported by local estradiol treatment. However, this estrogenic support is restricted to the early postnatal period, after which the morphology of SNB dendrites is insensitive to estrogens. To test if the developmentally restricted effects of estrogens on SNB dendrite growth coincide with the transient expression of ER in the target musculature, ERα expression was assessed during development and in adulthood. ERα expression in extra-Muscle fiber cells was greatest from postnatal day 7 (P7) to P14 and declined after P21. Because this pattern of ERα expression coincided with the period of estrogen-dependent dendrite growth, we tested if limiting hormone exposure to the period of maximal ERα expression in extra-muscle fiber cells could fully support estrogen-dependent SNB dendrite growth. We restricted estradiol treatment in castrated males from P7 to P21 and assessed SNB dendritic morphology at P28. Treating castrates with estradiol implants at the muscle from P7 to P21 supported dendrite growth to normal levels through P28. These data suggest that the transient ERα expression in target muscle could potentially define the critical period for estrogen-dependent dendrite growth in SNB motoneurons. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012.
    Developmental Neurobiology 01/2013; 73(1). DOI:10.1002/dneu.22040 · 3.37 Impact Factor
  • T. Verhovshek · L.M. Rudolph · D.R. Sengelaub ·
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    ABSTRACT: Neurotrophic factors and steroid hormones interact to regulate a variety of neuronal processes such as neurite outgrowth, differentiation, and neuroprotection. The coexpression of steroid hormone and neurotrophin receptor mRNAs and proteins, as well as their reciprocal regulation provides the necessary substrates for such interactions to occur. This review will focus on androgen brain-derived neurotrophic factor (BDNF) interactions in the spinal cord, describing androgen regulation of BDNF in neuromuscular systems following castration, androgen manipulation, and injury. Androgens interact with BDNF during development to regulate normally-occurring motoneuron death, and in adulthood, androgen–BDNF interactions are involved in the maintenance of several features of neuromuscular systems. Androgens regulate BDNF and trkB expression in spinal motoneurons. Androgens also regulate BDNF levels in the target musculature, and androgenic action at the muscle regulates BDNF levels in motoneurons. These interactions have important implications for the maintenance of motoneuron morphology. Finally, androgens interact with BDNF after injury, influencing soma size, dendritic morphology, and axon regeneration. Together, these findings provide further insight into the development and maintenance of neuromuscular systems and have implications for the neurotherapeutic/neuroprotective roles of androgens and trophic factors in the treatment of motoneuron disease and recovery from injury.
    Neuroscience 10/2012; 239:103–114. DOI:10.1016/j.neuroscience.2012.10.028 · 3.36 Impact Factor
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    ABSTRACT: During the postpartum period, women experience significant changes in their neuroendocrine profiles and social behavior compared to before pregnancy. A common experience with motherhood is a decrease in sexual desire. Although the lifestyle and peripheral physiological changes associated with parturition might decrease a woman's sexual interest, we hypothesized that there are also hormone-mediated changes in women's neural response to sexual and infant stimuli with altered reproductive priorities. We predicted that amygdala activation to sexually arousing stimuli would be suppressed in postpartum versus nulliparous women, and altered with intranasal oxytocin administration. To test this, we measured amygdala activation using fMRI in response to sexually arousing pictures, infant pictures, and neutral pictures in 29 postpartum and 30 nulliparous women. Half of the women received a dose of exogenous oxytocin before scanning. As predicted, nulliparous women subjectively rated sexual pictures to be more arousing, and infant pictures to be less arousing, than did postpartum women. However, nulliparous women receiving the nasal oxytocin spray rated the infant photos as arousing as did postpartum women. Right amygdala activation was lower in postpartum versus nulliparous women in response to sexual, infant, and neutral images, suggesting a generalized decrease in right amygdala responsiveness to arousing images with parturition. There was no difference in right amygdala activation with nasal spray application. Postpartum women therefore appear to experience a decrease in sexual interest possibly as a feature of a more generalized decrease in amygdala responsiveness to arousing stimuli.
    Hormones and Behavior 10/2012; 63(1). DOI:10.1016/j.yhbeh.2012.10.007 · 4.63 Impact Factor
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    ABSTRACT: The neuroendocrine state of new mothers may alter their neural processing of stressors in the environment through modulatory actions of oxytocin on the limbic system. We predicted that amygdala sensitivity to negatively arousing stimuli would be suppressed in postpartum compared to nulliparous women and that this suppression would be modulated by administration of oxytocin nasal spray. We measured brain activation (fMRI) and subjective arousal in response to negatively arousing pictures in 29 postpartum and 30 nulliparous women who received either oxytocin nasal spray or placebo before scanning. Pre- and post-exposure urinary cortisol levels were also measured. Postpartum women (placebo) demonstrated lower right amygdala activation in response to negative images, lower cortisol and lower negative photo arousal ratings to nulliparous women. Nulliparous women receiving oxytocin had lower right amygdala activation compared to placebo. Cortisol levels in the placebo group, and ratings of arousal across all women, were positively associated with right amygdala activation. Together, these findings demonstrate reductions in both amygdala activation and subjective negative arousal in untreated postpartum vs nulliparous women, supporting the hypothesis of an attenuated neural response to arousing stimuli in postpartum women. A causal role of oxytocin and the timing of potential effects require future investigation.
    Social Cognitive and Affective Neuroscience 09/2012; 9(1). DOI:10.1093/scan/nss100 · 7.37 Impact Factor
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    ABSTRACT: Treatment with testosterone is neuroprotective/neurotherapeutic after a variety of motoneuron injuries. Here we assessed whether testosterone might have similar beneficial effects after spinal cord injury (SCI). Young adult female rats received either sham or T9 spinal cord contusion injuries and were implanted with blank or testosterone-filled Silastic capsules. Four weeks later, motoneurons innervating the vastus lateralis muscle of the quadriceps were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Soma volume, motoneuron number, lesion volume, and tissue sparing were also assessed, as were muscle weight, fiber cross-sectional area, and motor endplate size and density. Contusion injury resulted in large lesions, with no significant differences in lesion volume, percent total volume of lesion, or spared white or gray matter between SCI groups. SCI with or without testosterone treatment also had no effect on the number or soma volume of quadriceps motoneurons. However, SCI resulted in a decrease in dendritic length of quadriceps motoneurons in untreated animals, and this decrease was completely prevented by treatment with testosterone. Similarly, the vastus lateralis muscle weights and fiber cross-sectional areas of untreated SCI animals were smaller than those of sham-surgery controls, and these reductions were both prevented by testosterone treatment. No effects on motor endplate area or density were observed across treatment groups. These findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be prevented by testosterone treatment, further supporting a role for testosterone as a neurotherapeutic agent in the injured nervous system.
    The Journal of Comparative Neurology 08/2012; 520(12):2683-96. DOI:10.1002/cne.23066 · 3.23 Impact Factor
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    ABSTRACT: Testosterone (T) regulates many traits related to fitness, including aggression. However, individual variation in aggressiveness does not always relate to circulating T, suggesting that behavioural variation may be more closely related to neural sensitivity to steroids, though this issue remains unresolved. To assess the relative importance of circulating T and neural steroid sensitivity in predicting behaviour, we measured aggressiveness during staged intrusions in free-living male and female dark-eyed juncos (Junco hyemalis). We compared aggressiveness to plasma T levels and to the abundance of androgen receptor (AR), aromatase (AROM) and oestrogen receptor alpha (ORα) mRNA in behaviourally relevant brain areas (avian medial amygdala, hypothalamus and song control regions). We also asked whether patterns of covariation among behaviour and endocrine parameters differed in males and females, anticipating that circulating T may be a better predictor of behaviour in males than in females. We found that circulating T related to aggressiveness only in males, but that gene expression for ORα, AR and AROM covaried with individual differences in aggressiveness in both sexes. These findings are among the first to show that individual variation in neural gene expression for three major sex steroid-processing molecules predicts individual variation in aggressiveness in both sexes in nature. The results have broad implications for our understanding of the mechanisms by which aggressive behaviour may evolve.
    Proceedings of the Royal Society B: Biological Sciences 06/2012; 279(1742):3547-55. DOI:10.1098/rspb.2012.0442 · 5.05 Impact Factor
  • Anna L Huguenard · Shannon M Fernando · D Ashley Monks · Dale R Sengelaub ·
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    ABSTRACT: The dendritic arbors of spinal motoneurons are dynamically regulated by a variety of factors, and several lines of evidence indicate that trophic interactions with the target musculature are of central importance. In highly androgen-sensitive motoneuron populations, androgens are thought to regulate motoneuron dendrites through their action at the receptor-enriched target musculature. Using rats transgenically modified to overexpress androgen receptor (AR) in skeletal muscle, we directly tested the hypothesis that the enhanced expression of AR in the target musculature can underlie the androgenic regulation of motoneuron dendritic morphology. The morphology of motoneurons innervating the quadriceps muscle was examined in wild-type (WT) rats as well as in rats that had been transgenically modified to overexpress ARs in their skeletal musculature. Motoneurons innervating the vastus lateralis muscle of the quadriceps in gonadally intact male rats, and castrated males with or without androgen replacement, were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. In WT rats, quadriceps motoneuron dendrites were insensitive to hormonal manipulation. In contrast, quadriceps motoneuron dendrites in gonadally intact transgenic males were larger than those of WT males. Furthermore, overexpression of ARs in the quadriceps muscle resulted in androgen sensitivity in dendrites, with substantial reductions in dendritic length occurring after castration; this reduction was prevented with testosterone replacement. Thus, it appears that the androgen sensitivity of motoneuron dendrites is conferred indirectly via the enrichment of ARs in the musculature.
    Endocrinology 02/2011; 152(2):639-50. DOI:10.1210/en.2010-1197 · 4.50 Impact Factor
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    Tom Verhovshek · Dale R Sengelaub ·
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    ABSTRACT: In adult male rats, androgens are necessary for the maintenance of the motoneurons and their target muscles of the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB) neuromuscular system, regulating motoneuron and muscle morphology, function, and expression of trophic factors. Castration of males results in somal, dendritic, and muscle atrophy as well as increases in brain-derived neurotrophic factor (BDNF) in the target musculature. Because BDNF can have either facilitative or inhibitory effects in other systems, we examined SNB neuromuscular morphology after BDNF blockade using a fusion protein (tyrosine kinase receptor type B IgG). Blockade of BDNF in gonadally intact males resulted in hypertrophy of SNB motoneuron dendrites and target musculature, suggesting that normal levels of BDNF are inhibitory in SNB neuromuscular system. BDNF blockade in castrated males prevented SNB motoneuron atrophy and attenuated target muscle weight loss. This is the first demonstration that the highly androgen-sensitive SNB motoneuron dendrites and target muscles can be maintained in the absence of gonadal hormones and, furthermore, that blocking BDNF can have trophic effects on skeletal muscle. These results suggest that whereas BDNF is involved in the signaling cascade mediating the androgenic support of SNB neuromuscular morphology, its action can be inhibitory. Furthermore, the elevations in BDNF after castration may be responsible for the castration-induced atrophy in SNB motoneurons and target muscles, and the trophic effects of androgens may be mediated in part through a suppression of BDNF. These results may have relevance to therapeutic approaches to the treatment of neurodegenerative disease or myopathies.
    Endocrinology 11/2010; 151(11):5337-48. DOI:10.1210/en.2010-0799 · 4.50 Impact Factor
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    Kathryn M Lenz · Dale R Sengelaub ·
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    ABSTRACT: Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking results in decreased motoneuron number, size, and dendritic length in the adult SNB, as well as deficits in adult male copulatory behavior. Our previous findings that licking-like tactile stimulation influences SNB dendritic development and upregulates Fos expression in the lumbosacral spinal cord suggest that afferent signaling is changed by differences in maternal stimulation. Oxytocin afferents from the hypothalamus are a possible candidate, given previous research that has shown oxytocin is released following sensory stimulation, oxytocin modulates excitability in the spinal cord, and is a pro-erectile modulator of male sex behavior. In this experiment, we used immunofluorescence and immediate early gene analysis to assess whether licking-like tactile stimulation of the perineum activated parvocellular oxytocinergic neurons in the hypothalamus in neonates. We also used enzyme immunoassay to determine whether this same stroking stimulation produced an increase in spinal oxytocin levels. We found that stroking increased Fos immunolabeling in small oxytocin-positive cells in the paraventricular nucleus of the hypothalamus, in comparison to unstroked or handled control pups. In addition, 60s of licking-like perineal stimulation produced a transient 89% increase in oxytocin levels in the lumbosacral spinal cord. Together, these results suggest that oxytocin afferent activity may contribute to the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior.
    Hormones and Behavior 09/2010; 58(4):575-81. DOI:10.1016/j.yhbeh.2010.07.010 · 4.63 Impact Factor

Publication Stats

4k Citations
427.08 Total Impact Points


  • 1987-2015
    • Indiana University Bloomington
      • • Department of Psychological and Brain Sciences
      • • Department of Biology
      Bloomington, Indiana, United States
  • 1981-1986
    • Cornell University
      • Department of Psychology
      Итак, New York, United States