D W Pfaff

The Rockefeller University, New York City, New York, United States

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Publications (671)2914.9 Total impact

  • Sara M Schaafsma, Donald W Pfaff
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    ABSTRACT: The male predominance of autism spectrum disorders (ASD) is one of the best-known, and at the same time, one of the least understood characteristics of these disorders. In this paper we review genetic, epigenetic, hormonal, and environmental mechanisms underlying this male preponderance. Sex-specific effects of Y-linked genes (including SRY expression leading to testicular development), balanced and skewed X-inactivation, genes that escape X-inactivation, parent-of-origin allelic imprinting, and the hypothetical heterochromatin sink are reviewed. These mechanisms likely contribute to etiology, instead of being simply causative to ASD. Environments, both internal and external, also play important roles in ASD's etiology. Early exposure to androgenic hormones and early maternal immune activation comprise environmental factors affecting sex-specific susceptibility to ASD. The gene-environment interactions underlying ASD, suggested here, implicate early prenatal stress as being especially detrimental to boys with a vulnerable genotype.
    Frontiers in Neuroendocrinology 04/2014; · 7.99 Impact Factor
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    ABSTRACT: This theoretical paper proposes that underlying the concept of libido is a primitive set of brain mechanisms responsible for the generalized arousal of the central nervous system and the activation of all behavioral responses. Having given the concept of “generalized CNS arousal” an operational definition, we write an equation that describes how specific motivational needs are integrated with generalized arousal to produce an overall state of the CNS sufficient for potentiating behavioral responses. Factor analysis of behavioral data with mice suggests that among all CNS arousal-related influences, generalized arousal contributes about a third of the variance. Many neuroanatomical, neurophysiological, and genomic mechanisms for arousal are reviewed here. Highlighted are large reticular formation neurons in the medullary medulla whose axons bifurcating rostrally and caudally equip them to contribute, respectively, both to cerebral cortical arousal and to autonomic arousal. Their rapid responses would cause sudden changes in CNS state associated with, for example, states of panic. Consequences of the actions of generalized arousal networks include increased alertness and attention that serve all cognitive functions and all emotional expression. Specifically with respect to psychoanalytic concepts, these networks provide the psychic energy necessary for the expression of libido.
    Neuropsychoanalysis: An Interdisciplinary Journal for Psychoanalysis and the Neurosciences. 01/2014; 9(2):173-181.
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    ABSTRACT: Background Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Method Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity x frequency of exercise, age, and education abstained from exercise for 24 hours prior to testing and provided 24-hour cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image. Results Between group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence. Conclusion The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.
    Drug and Alcohol Dependence 01/2014; · 3.14 Impact Factor
  • Sara M. Schaafsma, Donald W. Pfaff
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    ABSTRACT: The male predominance of autism spectrum disorders (ASD) is one of the best-known, and at the same time, one of the least understood characteristics of these disorders. In this paper we review genetic, epigenetic, hormonal, and environmental mechanisms underlying this male preponderance. Sex-specific effects of Y-linked genes (including SRY expression leading to testicular development), balanced and skewed X-inactivation, genes that escape X-inactivation, parent-of-origin allelic imprinting, and the hypothetical heterochromatin sink are reviewed. These mechanisms likely contribute to etiology, instead of being simply causative to ASD. Environments, both internal and external, also play important roles in ASD’s etiology. Early exposure to androgenic hormones and early maternal immune activation comprise environmental factors affecting sex-specific susceptibility to ASD. The gene-environment interactions underlying ASD, suggested here, implicate early prenatal stress as being especially detrimental to boys with a vulnerable genotype.
    Frontiers in Neuroendocrinology 01/2014; · 7.99 Impact Factor
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    ABSTRACT: While many physiological effects of estrogens (E) are due to regulation of gene transcription by liganded estrogen receptors (ER), several effects are also mediated, at least in part, by rapid non-genomic actions of E. Though the relative importance of rapid versus genomic effects in the central nervous system is controversial, we showed previously that membrane-limited effects of E, initiated by an estradiol bovine serum albumin conjugate (E2-BSA), could potentiate transcriptional effects of 17ß-estradiol from an estrogen response element (ERE)-reporter in neuroblastoma cells. Here, using specific inhibitors and activators in a pharmacological approach, we show that activation of phosphatidylinositol-3-phosphate kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways, dependent on a Gaq coupled receptor signaling are important in this transcriptional potentiation. We further demonstrate, using ERa phospho-deficient mutants, that E2-BSA mediated phosphorylation of ERa is one mechanism to potentiate transcription from an ERE reporter construct. This study provides a possible mechanism by which signaling from the membrane is coupled to transcription in the nucleus, providing an integrated view of hormone signaling in the brain.
    The Journal of steroid biochemistry and molecular biology 10/2013; · 2.66 Impact Factor
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    ABSTRACT: Expression of the primary female sex behaviour, lordosis, in laboratory animals depends on oestrogen-induced expression of progesterone receptor (PgR) within a defined cell group in the ventrolateral portion of the ventromedial nucleus of the hypothalamus (VMH). The minimal latency from oestradiol administration to lordosis is 18 hours. During that time, ligand-bound oestrogen receptors (ER), members of a nuclear receptor superfamily, recruit transcriptional coregulators, which induce covalent modifications of histone proteins thus leading to transcriptional activation or repression of target genes. The aim of this study was to investigate early molecular epigenetic events underlying oestrogen-regulated transcriptional activation of the Pgr gene in the VMH of female mice. Oestradiol (E2) administration induced rapid and transient global histone modifications in the VMH of ovariectomised female mice. Histone H3 N-terminus phosphorylation (H3S10phK14Ac), acetylation (H3Ac) and methylation (H3K4me3) exhibited distinct temporal patterns facilitative to the induction of transcription; and a transcriptional repressive (H3K9me3) modification showed a different temporal pattern. Collectively these should create a permissive environment for the transcriptional activity necessary for lordosis, within 3-6 hours after E2-treatment. In the VMH, changes in the H3Ac and H3K4me3 levels of histone H3 were also detected at the promoter region of Pgr gene within the same time window, but were delayed in the preoptic area. Moreover, examination of histone modifications associated with the promoter of another ER-target gene, oxytocin receptor (Oxtr), revealed gene- and brain-region specific effects of E2 treatment. In the VMH of female mice, E2-treatment resulted in the recruitment of ERα to the oestrogen-response-elements-containing putative enhancer site of Pgr gene ~200kb upstream of the transcription start site (TSS), but failed to increase ERα association with the more proximal promoter region. Finally, E2 administration led to significant changes in the mRNA expression of several ER coregulators in a brain-region dependent manner. Taken together, these data indicate that in the hypothalamus and preoptic area of female mice, early responses to E2-treatment involve highly specific changes in chromatin structure, dependent on cell group, gene, histone modification studied, promoter/enhancer site and time following E2. This article is protected by copyright. All rights reserved.
    Journal of Neuroendocrinology 08/2013; · 3.33 Impact Factor
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    ABSTRACT: The endocannabinoid (eCB) system regulates emotion, stress, memory and cognition through the CB1 receptor. In order to test the role of CB1 signaling in social anxiety and memory, we utilized a genetic knockout (KO) and a pharmacological approach. Specifically, we assessed the effects of a constitutive KO of CB1 receptors (CB1 KOs) and systemic administration of a CB1 antagonist (AM251; 5 mg/kg) on social anxiety in a social investigation paradigm and social memory in a social discrimination test. Results showed that when compared to wildtypes (WT) and vehicle-treated animals, CB1 KOs and WT animals that received an acute dose of AM251 displayed anxiety-like behaviors toward a novel male conspecific. When compared to WT animals, KOs showed both active and passive defensive coping behaviors; i.e. elevated avoidance, freezing and risk-assessment behaviors, all consistent with an anxiety-like profile. Animals that received acute doses of AM251 also showed an anxiety-like profile when compared to vehicle treated animals, yet did not show an active coping strategy i.e. changes in risk-assessment behaviors. In the social discrimination test, CB1 KOs and animals that received the CB1 antagonist showed enhanced levels of social memory relative to their respective controls. These results clearly implicate CB1 receptors in the regulation of social anxiety, memory and arousal. The elevated arousal/ anxiety resulting from either total CB1 deletion or an acute CB1 blockade may promote enhanced social discrimination/memory. These findings may emphasize the role of the eCB system in anxiety and memory to affect social behavior.
    Genes Brain and Behavior 05/2013; · 3.60 Impact Factor
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    ABSTRACT: Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRα and TRβ. The loss of TRα1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRα1 knockout (α1KO) and TRβ (βKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRα1 and TRβ, in the regulation of state anxiety, with α1 knockout animals (α1KO) showing higher levels of anxiety and βKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, α1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in α1KO male mice. These behaviors support the idea that TRα1 could be inhibitory to ERα driven transcription that ultimately impacts ERα driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle.
    Hormones and Behavior 04/2013; · 3.74 Impact Factor
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    Richard G Hunter, Bruce S McEwen, Donald W Pfaff
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    ABSTRACT: We recently reported that acute stress causes a substantial upregulation of the epigenetic mark, Histone H3 Lysine 9 Trimethyl (H3K9me3) in the rat hippocampus within an hour of acute stress exposure. To determine the function of this change we used ChIP-sequencing to determine where this silencing mark was being localized. We found that it showed a strong bias toward localization at more active classes of retrotransposable elements and away from genes. Further, we showed that the change was functional in that it reduced transcription of some of these elements (notably the endogenous retrovirus IAP and the B2 SINE). In this commentary we examine these results, which appear to describe a selective genomic stress response and relate it to human health and disease, particularly stress related maladies such as Post-traumatic Stress Disorder, which have recently been shown to have both epigenetic elements in their causation as well as differences in epigenetic marking of retrotransposons in human patients.
    Mobile genetic elements. 03/2013; 3(2):e24555.
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    ABSTRACT: The hippocampus is a highly plastic brain region particularly susceptible to the effects of environmental stress; it also shows dynamic changes in epigenetic marks in response to stress and learning. We have previously shown that, in the rat, acute (30 min) restraint stress induces a substantial, regionally specific, increase in hippocampal levels of the repressive histone H3 lysine 9 trimethylation (H3K9me3). Because of the large magnitude of this effect and the fact that stress can induce the expression of endogenous retroviruses and transposable elements in many systems, we hypothesized that the H3K9me3 response was targeted to these elements as a means of containing potential genomic instability. We used ChIP coupled with next generation sequencing (ChIP-Seq) to determine the genomic localization of the H3K9me3 response. Although there was a general increase in this response across the genome, our results validated this hypothesis by demonstrating that stress increases H3K9me3 enrichment at transposable element loci and, using RT-PCR, we demonstrate that this effect represses expression of intracisternal-A particle endogenous retrovirus elements and B2 short interspersed elements, but it does not appear to have a repressive effect on long interspersed element RNA. In addition, we present data showing that the histone H3K9-specific methyltransferases Suv39h2 is up-regulated by acute stress in the hippocampus, and that this may explain the hippocampal specificity we observe. These results are a unique demonstration of the regulatory effect of environmental stress, via an epigenetic mark, on the vast genomic terra incognita represented by transposable elements.
    Proceedings of the National Academy of Sciences 10/2012; 109(43):17657-17662. · 9.74 Impact Factor
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    ABSTRACT: The medial preoptic area has been shown to be intricately involved in many behaviors, including locomotion, sexual behavior, maternal care, and aggression. The gene encoding estrogen receptor-α (ERα) protein is expressed in preoptic area neurons, and a very dense immunoreactive field of ERα is found in the preoptic region. ERα knockout animals show deficits in maternal care and sexual behavior and fail to exhibit increases in these behaviors in response to systemic estradiol treatment. In the present study, we used viral-vector mediated RNA interference to silence ERα expression specifically in the preoptic area of female mice and measured a variety of behaviors, including social and sexual aggression, maternal care, and arousal activity. Suppression of ERα in the preoptic area almost completely abolished maternal care, significantly increasing the latency to pup retrieval and significantly reducing the time the moms spent nursing and licking the pups. Strikingly, maternal aggression toward a male intruder was not different between control and preoptic ERα-silenced mice, demonstrating the remarkably specific role of ERα in these neurons. Reduction of ERα expression in preoptic neurons significantly decreased sexual behavior in female mice and increased aggression toward both sexual partners and male intruders in a seminatural environment. Estrogen-dependent increases in arousal, measured by home cage activity, were not mediated by ERα expression in the preoptic neurons we targeted, as ERα-suppressed mice had increases similar to control mice. Thus, we have established that a specific gene in a specific group of neurons is required for a crucially important natural behavior.
    Proceedings of the National Academy of Sciences 09/2012; 109(40):16324-9. · 9.74 Impact Factor
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    ABSTRACT: Typically one expects that the intervals between consecutive occurrences of a particular behavior will have a characteristic time scale around which most observations are centered. Surprisingly, the timing of many diverse behaviors from human communication to animal foraging form complex self-similar temporal patterns reproduced on multiple time scales. We present a general framework for understanding how such scale invariance may arise in nonequilibrium systems, including those that regulate mammalian behaviors. We then demonstrate that the predictions of this framework are in agreement with detailed analysis of spontaneous mouse behavior observed in a simple unchanging environment. Neural systems operate on a broad range of time scales, from milliseconds to hours. We analytically show that such a separation between time scales could lead to scale-invariant dynamics without any fine tuning of parameters or other model-specific constraints. Our analyses reveal that the specifics of the distribution of resources or competition among several tasks are not essential for the expression of scale-free dynamics. Rather, we show that scale invariance observed in the dynamics of behavior can arise from the dynamics intrinsic to the brain.
    Proceedings of the National Academy of Sciences 06/2012; 109(26):10564-9. · 9.74 Impact Factor
  • Donald W Pfaff, Eugene M Martin, Donald Faber
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    ABSTRACT: The existence of a primitive CNS function involved in the activation of all vertebrate behaviors, generalized arousal (GA), has been proposed. Here, we provide an overview of the neuroanatomical, neurophysiological and molecular properties of reticular neurons within the nucleus gigantocellularis (NGC) of the mammalian medulla, and propose that the properties of these neurons equip them to contribute powerfully to GA. We also explore the hypothesis that these neurons may have evolved from the Mauthner cell in the medulla of teleost fish, although NGC neurons have a wider range of action far beyond the specific escape network served by Mauthner cells. Understanding the neuronal circuits that control and regulate GA is central to understanding how motivated behaviors such as hunger, thirst and sexual behaviors arise.
    Trends in Neurosciences 05/2012; 35(8):468-76. · 13.58 Impact Factor
  • A W Quinkert, D W Pfaff
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    ABSTRACT: Deep brain stimulation (DBS) has shown promise in the treatment of many neurological and psychiatric disorders as well as a disorder of consciousness, the minimally conscious state (MCS). In the clinic, DBS is always monotonic standard pulses; however, we have hypothesized that temporally patterned pulses might be more efficient in achieving desired behavioral responses. Here we present two experiments on DBS of the central thalamus to increase arousal, as measured by motor activity, and to affect the electroencephalogram (EEG). In the first, we optimized amplitude and frequency in standard stimulation of the central thalamus in intact mice. In the second, the optimized fixed frequency was compared to two alternative temporal patterns, chaotic and random, which were physically identical to each other and fixed frequency in all ways except temporal pattern. In both experiments and with all types of stimulation, DBS of the central thalamus increased arousal as measured by motor activity. These data also revealed that temporal patterning of pulses can modulate response to stimulation. That temporal patterns in DBS of the central thalamus were found to alter motor activity response implies possible usefulness of temporal patterns in DBS of other contexts. More investigation into exactly how temporally patterned stimulation may affect neuronal circuit dynamics is necessary.
    Behavioural brain research 04/2012; 229(2):349-58. · 3.22 Impact Factor
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    ABSTRACT: Ovariectomized females were given an infusion in the medial preoptic area (MPOA) of a viral vector carrying either a shRNA directed against the estrogen receptor α (ERα) or luciferase. The females were subjected to a test for sexual incentive motivation immediately followed by a test for receptivity and proceptive behaviors. Two weeks later they were tested in the light/dark choice procedure, and after another 2 weeks they were subjected to a test in a brightly lit open field. Finally, the females were given free access to a running wheel for 88h. The females were treated with estradiol benzoate (EB), 18 or 1.5μg/kg, in randomized order 52h before each test except the running wheel. In that experiment, they were given EB 48h after introduction into the wheel cage. They were given progesterone, 1mg/rat, about 4h before all tests, except the running wheel. The shRNA reduced the number of ERα with 83%. Females with few ERα in the MPOA showed increased lordosis quotient after the 1.5μg/kg dose of EB. There was no effect on proceptive behaviors or on rejections. When given the 18μg/kg EB dose, there was no difference between females with few preoptic ERα and controls. In the test for sexual incentive motivation, females with few preoptic ERα approached the castrated male incentive more than controls, regardless of EB dose. They also moved a shorter distance. In the light/dark choice test as well as in the open field, females with few ERα in the MPOA showed signs of reduced fear/anxiety, since they spent more time in the light part of the dark/light box and in the center of the open field. Finally, the data from the running wheel showed that females with few preoptic ERα failed to show enhanced activity after treatment with EB. These data show that the preoptic ERα inhibits lordosis in females with an intermediate level of receptivity while it fails to do so in fully receptive females. The ERα in the MPOA seems to be necessary for selective approach to a sexual incentive. Finally, activation of this receptor appears to have anxiogenic effects in the procedures employed here. A hypothesis for how all these actions of the preoptic ERα contributes to efficient reproductive behavior is outlined.
    Behavioural brain research 02/2012; 230(1):11-20. · 3.22 Impact Factor
  • Bin Wang, Junhui Ni, Yoav Litvin, Donald W Pfaff, Qiao Lin
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    ABSTRACT: We present an innovative microfluidic approach to transcranial delivery of small quantities of drugs in brief time pulses for neurobiological studies. The approach is based on a two-stage process of consecutive drug dispensing and delivery, demonstrated by a device featuring a fully planar design in which the microfluidic components are integrated in a single layer. This 2-D configuration offers ease in device fabrication and is compatible to diverse actuation schemes. A compliance-based and normally closed check valve is used to couple the microchannels that are responsible for drug dispensing and delivery. Brief pneumatic pressure pulses are used to mobilize buffer and drug solutions, which are injected via a cannula into brain tissue. Thus, the device can potentially allow transcranial drug delivery and can also be potentially extended to enable transdermal drug delivery. We have characterized the device by measuring the dispensed and delivered volumes under varying pneumatic driving pressures and pulse durations, the standby diffusive leakage, and the repeatability in the delivery of multiple pulses of drug solutions. Results demonstrate that the device is capable of accurately dispensing and delivering drug solutions 5 to 70 nL in volume within time pulses as brief as 50 ms, with negligible diffusive drug leakage over a practically relevant time scale. Furthermore, testing of pulsatile drug delivery into intact mouse brain tissue has been performed to demonstrate the potential application of the device to neurobiology.
    Journal of Microelectromechanical Systems 02/2012; 21(1). · 2.13 Impact Factor
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    ABSTRACT: Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice.
    Physiology & Behavior 11/2011; 105(4):915-24. · 3.16 Impact Factor
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    Alan Leshner, Donald W Pfaff
    Proceedings of the National Academy of Sciences 09/2011; 108 Suppl 3:15537-41. · 9.74 Impact Factor
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    ABSTRACT: To better understand the precise role of sensory corpuscles within the female external genitalia. After IRB approval, waste tissue samples were obtained from 10 normal girls (aged 2-9 years) who underwent surgery for labial fusion. Immunocytochemistry against protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), 5-hydroxytryptamine transporter (5HTT), 5-hydroxytryptamine receptor 1A (5HT1A), Neuronal Peptide Y (NPY), neuronal nitric oxide synthase (nNOS), and estrogen receptors (ER) α and β was performed. Pacinian-like corpuscles were identified in epithelium of labia minora of prepubertal girls. A central structure composed of an axon surrounded by a central core, outer core, external capsule, surrounded by encapsulated stroma, and a subsidiary innervation in the outer aspect of the corpuscle stroma stained for PGP 9.5 in the outer core and layers of the external capsule, NSE positive cells in layers of the outer core, 5HTT in stroma of the corpuscle and cells located in layers of the outer core, 5HT1A in cells of outer core, NPY in stroma of the corpuscle, and nNOS in external core and external capsule of the central structure. ERα was present in stroma, external core, and external capsule, and ERβ in stroma of the corpuscle with subsidiary innervation in the stroma positive to PGP 9.5, VIP, and NPY. PGP 9.5, NSE, ERα, nNOS, and 5HTT immunoreaction detected in the outer core and external capsule could indicate these areas may play an important role in the functional aspects of the Pacinian-like corpuscle.
    Journal of pediatric and adolescent gynecology 09/2011; 24(6):353-8. · 0.90 Impact Factor

Publication Stats

20k Citations
2,914.90 Total Impact Points

Institutions

  • 1975–2014
    • The Rockefeller University
      • Laboratory of Neurobiology and Behavior
      New York City, New York, United States
  • 2013
    • University of Massachusetts Boston
      • Department of Psychology
      Boston, MA, United States
  • 2008–2013
    • Tulane University
      • Department of Cell and Molecular Biology
      New Orleans, LA, United States
    • Columbia University
      • Department of Psychology
      New York City, NY, United States
  • 2008–2012
    • Universitetet i Tromsø
      • Department of Psychology
      Tromsø, Troms Fylke, Norway
  • 2001–2012
    • Weill Cornell Medical College
      • • Department of Anesthesiology
      • • Department of Neurological Surgery
      • • Department of Psychiatry
      New York City, NY, United States
  • 2011
    • American Association for the Advancement of Science
      Washington, Washington, D.C., United States
  • 2009–2011
    • Mount Sinai School of Medicine
      • • Department of Psychiatry
      • • Department of Pharmacology and Systems Therapeutics
      Manhattan, New York, United States
    • University of São Paulo
      • Faculdade de Medicina de Ribeirão Preto (FMRP)
      São Paulo, Estado de Sao Paulo, Brazil
  • 2004–2011
    • University of Guelph
      • Department of Psychology
      Guelph, Ontario, Canada
    • University of Texas at Austin
      • Department of Integrative Biology
      Texas City, TX, United States
    • University of Occupational and Environmental Health
      • Department of Physiology
      Kitakyūshū, Fukuoka, Japan
    • American Congress of Obstetricians and Gynecologists
      Washington, Washington, D.C., United States
  • 2009–2010
    • Wellesley College
      Wellesley, Massachusetts, United States
  • 2002–2010
    • Cornell University
      • • Department of Neurology and Neuroscience
      • • Department of Psychiatry
      Ithaca, NY, United States
  • 2003–2008
    • The University of Western Ontario
      • • Department of Psychology
      • • Department of Statistical and Actuarial Sciences
      London, Ontario, Canada
  • 2005–2007
    • Pennsylvania State University
      • • Department of Physics
      • • Department of Biology
      University Park, MD, United States
  • 2006
    • New York University
      • Department of Psychology
      New York City, NY, United States
    • Kagoshima University
      • Faculty of Law, Economics and the Humanities
      Kagosima, Kagoshima, Japan
  • 1976–2006
    • CUNY Graduate Center
      New York City, New York, United States
  • 1999
    • Fordham University
      • Department of Psychology
      New York City, NY, United States
  • 1998
    • National Institutes of Health
      • Section on Molecular Neurobiology
      Bethesda, MD, United States
  • 1981–1998
    • University of Illinois at Chicago
      • Department of Anatomy and Cell Biology (Chicago)
      Chicago, IL, United States
  • 1997
    • University of Rochester
      • Department of Brain and Cognitive Sciences
      Rochester, NY, United States
  • 1995
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
    • Fisheries Research Agency
      Yokohama, Kanagawa, Japan
    • University of Maryland, Baltimore
      • Department of Physiology
      Baltimore, MD, United States
    • Nippon Medical School
      • Department of Physiology
      Tokyo, Tokyo-to, Japan
  • 1994
    • Concordia University Montreal
      • Department of Psychology
      Montréal, Quebec, Canada
    • University of Pittsburgh
      • Pharmacy and Therapeutics
      Pittsburgh, PA, United States
  • 1989
    • Università della Calabria
      Rende, Calabria, Italy