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Cited by 53Neuroendocrine regulation and behaviorSexual Differentiation and DisordersGenetics and Neurodevelopmental Disorders

The Nuclear Receptor Corepressor Has Organizational Effects within the Developing Amygdala on Juvenile Social Play and Anxiety-Like Behavior

Open access
Jessen, Heather M., Kolodkin, Mira H., Bychowski, Meaghan E., Auger, Catherine J., Auger, Anthony P.·2010·Endocrinology
DOI 10.1210/en.2009-0594PMC PMC2840691
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Abstract

Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior. We used real-time PCR to show that NCoR mRNA levels are sexually dimorphic, that females express higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and that NCoR mRNA levels are reduced by estradiol treatment. To investigate the functional role of NCoR on juvenile social behavior, we infused small interfering RNA targeted against NCoR within the developing rat amygdala and assessed the enduring impact on juvenile social play behavior, sociability, and anxiety-like behavior. As expected, control males exhibited higher levels of juvenile social play than control females. Reducing NCoR expression during development further increased juvenile play in males only. Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females. These data suggest that the corepressor NCoR functions to blunt sex differences in juvenile play behavior, a sexually dimorphic and hormone-dependent behavior, and appears critical for appropriate anxiety-like behavior in juvenile males and females.

AI snapshot

Written from the paper’s full text.

TL;DR

NCoR mRNA is sexually dimorphic in the developing rat amygdala and hypothalamus, with females expressing higher levels that are reduced by estradiol. Transient neonatal amygdala NCoR knockdown increased juvenile social play in males and increased anxiety-like behavior in both males and females.

Key findings

  • On postnatal day 1 (PN1), females expressed higher NCoR mRNA than males in the medial-basal hypothalamus (MBH) (P < 0.05; n = 4 males, 5 females) and amygdala (P < 0.05; n = 8 males, 11 females).
  • Estradiol benzoate treatment (100 µg on PN0) reduced NCoR mRNA in females to male-like levels in both MBH and amygdala (P < 0.01, ANOVA; P < 0.05, Tukey’s post hoc).
  • NCoR siRNA infused into the developing amygdala decreased NCoR mRNA in males and females (P < 0.05), did not significantly affect MBH NCoR or SMRT mRNA, and was transient (no significant difference at PN10).
  • Control males showed higher juvenile social play than control females (P < 0.001); NCoR siRNA-treated males showed higher play than control males (P < 0.05), with no effect in females. NCoR siRNA increased anxiety-like behavior in the elevated plus maze (P < 0.05) and light/dark box (P < 0.01) in both sexes, while sociability remained normal in all groups.

Methods

  • Sprague Dawley rats were used; PN1 brain tissue was microdissected for real-time PCR of NCoR and SMRT in MBH and amygdala, with separate animals receiving PN0 estradiol benzoate or sesame oil.
  • NCoR or nonsense control siRNA was infused bilaterally into the neonatal amygdala at 12 h and 28 h after birth; knockdown was confirmed by PCR, and behavior was tested at PN25–29 for juvenile social play, PN32 for sociability, PN34 for elevated plus maze, and then light/dark chamber.
  • Data were analyzed with two-tailed t tests, one-way or two-way ANOVA with Tukey’s post hoc tests, and repeated-measures ANOVA for sociability; behavioral scoring was blind to treatment.

Limitations

  • Stated: it remains to be determined whether the effects occur via NCoR’s association with nuclear receptor complexes, methyl-binding proteins, or both.
  • Evident: the siRNA effect is transient and targeted to the neonatal amygdala, and no adult behavioral outcomes are reported, so persistence beyond the juvenile period is not established.
  • Evident: some groups have modest sample sizes, no direct protein/function measure is reported, and the downstream genes mediating the behavioral effects are not identified.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1210/en.2009-0594

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

13 of 38 cited sources checked · 11 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Juvenile social play behavior is influenced by neonatal estradiol and testosterone exposure.

    “This difference is known to be influenced by neonatal estradiol and testosterone exposure, because manipulating these hormone levels can sex reverse differences in juvenile social play behavior in rats (6 -8) and nonhuman primates (9,10).”
    Quote in the paperSubstantial claim1 of 5 sources checked
    • cites [6] Meaney, 1981, Neonatal-androgens influence the social play of prepubescent rats., Horm Behav source
    • cites [7] Beatty, 1981, Temporal boundary of the sensitive period for hormonal organization of social play in juvenile rats., Physiol Behav source
    • cites [8] Olesen, 2005, Dopaminergic activation of estrogen receptors in neonatal brain alters progestin receptor expression and juvenile social play behavior., Endocrinology source
    • cites [9] Goy, 1996, The effects of diethylstilbestrol (DES) before birth on the development of masculine behavior in juvenile female rhesus monkeys., Horm Behav source
    • cites [10] Wallen, 2005, Hormonal influences on sexually differentiated behavior in nonhuman primates., Front Neuroendocrinol source
  • Premisecitation

    NCoR appears to interact with both androgen and estrogen receptors.

    “Because NCoR appears to interact with both androgen (19,20) and estrogen receptors (21), it is possible that reducing NCoR expression enhances the function of both nuclear receptors to further masculinize juvenile social play.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [19] Cheng, 2002, Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor., Mol Endocrinol source
    • cites [20] Yoon, 2006, The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor., Mol Endocrinol source
    • cites [21] Lavinsky, 1998, Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes., Proc Natl Acad Sci USA source
  • Findingown data

    Targeted decrease in NCoR expression in the developing amygdala increases anxiety-like behavior in juvenile male and female rats.

    “A targeted decrease in NCoR expression within the developing amygdala was found to significantly increase anxiety-like behavior during the juvenile period in males and females.”
    • Also stated in: § Abstract · plain
      “Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females.”
    Quote in the paperSubstantial claim
  • Findingown data

    Infusion of NCoR siRNA into the developing amygdala decreases NCoR mRNA levels in male and female rats.

    “NCoR siRNA infused into the developing amygdala was confirmed to decrease the levels of NCoR mRNA in males and females (P Ͻ 0.05, t test; Fig. 2, A and B).”
    Quote in the paperSubstantial claim
  • Findingown data

    On postnatal day 1, female rats express higher levels of NCoR mRNA than males in the amygdala.

    “Females were also found to express higher levels of NCoR mRNA within the amygdala on PN1 (P Ͻ 0.05, t test, Fig. 1B).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 21
  • May combine two claims. 12
  • The quote only partly states this claim. 2

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NCoR is a corepressor for androgen and estrogen receptors.

    “Since then, it has been shown to be a corepressor molecule for androgen and estrogen receptors (19 -21).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [19] Cheng, 2002, Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor., Mol Endocrinol source
    • cites [20] Yoon, 2006, The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor., Mol Endocrinol source
    • cites [21] Lavinsky, 1998, Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes., Proc Natl Acad Sci USA source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Estradiol can down-regulate NCoR expression in vitro.

    “These data are consistent with previously published in vitro data showing that estradiol can down-regulate NCoR expression (38)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [38] Frasor, 2005, Estrogen down-regulation of the corepressor N-CoR: mechanism and implications for estrogen derepression of N-CoR-regulated genes., Proc Natl Acad Sci USA source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Compensatory mechanisms to reduce overt sex differences in some behaviors have been proposed previously.

    “Compensatory mechanisms to reduce overt sex differences in some behaviors have been proposed previously (40,41), and it is possible that NCoR may be a molecule involved in reducing some sex differences in social play behavior.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [40] De Vries, 2004, Minireview: sex differences in adult and developing brains: compensation, compensation, compensation., Endocrinology source
    • cites [41] McCarthy, 2005, When is a sex difference not a sex difference?, Front Neuroendocrinol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NCoR can also repress gene expression via its interactions with methyl-binding proteins, such as Kaiso and MeCP2.

    “Given that NCoR disruption increases juvenile anxiety-like behavior in both males and females, it is important to consider that NCoR can also repress gene expression via its interactions with methyl-binding proteins, such as Kaiso (22) and MeCP2 (23,24).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [22] Yoon, 2003, N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso., Mol Cell source
    • cites [23] Cukier, 2008, Genetic modifiers of MeCP2 function in Drosophila, PLoS Genet source
    • cites [24] Kokura, 2001, The Ski protein family is required for MeCP2-mediated transcriptional repression., J Biol Chem source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Juvenile social play behavior is classically thought to be due to activation of androgen receptors, with some data suggesting a possible involvement of estrogen receptors.

    “Juvenile social play behavior is classically thought to be due to activation of androgen receptors (6,32), with some data suggesting a possible involvement of estrogen receptors (8).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [6] Meaney, 1981, Neonatal-androgens influence the social play of prepubescent rats., Horm Behav source
    • cites [32] Meaney, 1986, Testosterone implants into the amygdala during the neonatal period masculinize the social play of juvenile female rats., Brain Res source
    • cites [8] Olesen, 2005, Dopaminergic activation of estrogen receptors in neonatal brain alters progestin receptor expression and juvenile social play behavior., Endocrinology source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Coactivators are critical in mediating sexual differentiation of the brain.

    “These results are also interesting when considered with findings suggesting that coactivators are critical in mediating sexual differentiation of the brain (14,17).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [14] Auger, 2002, Expression of the nuclear receptor coactivator, cAMP response element-binding protein, is sexually dimorphic and modulates sexual differentiation of neonatal rat brain., Endocrinology source
    • cites [17] Auger, 2000, Steroid receptor coactivator-1 (SRC-1) mediates the development of sex-specific brain morphology and behavior., Proc Natl Acad Sci USA source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    There is evidence that NCoR can interact directly with methyl-binding proteins or indirectly via its interaction with the Sin3 corepressor complex.

    “Although numerous corepressors have been identified that interact with methyl-binding proteins, there is evidence that NCoR can interact directly with methyl-binding proteins (22)(23)(24) or indirectly via its interaction with the Sin3 corepressor complex (36).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [22] Yoon, 2003, N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso., Mol Cell source
    • cites [23] Cukier, 2008, Genetic modifiers of MeCP2 function in Drosophila, PLoS Genet source

      The Discussion (page unavailable) says MeCP2 associates with a corepressor complex containing Sin3A. The Results identify a Drosophila N-CoR homolog as a genetic modifier of MeCP2, but our copy does not say that N-CoR interacts with Sin3A or reaches MeCP2 indirectly through that complex. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [24] Kokura, 2001, The Ski protein family is required for MeCP2-mediated transcriptional repression., J Biol Chem source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    MeCP2 has been shown to directly interact with Sin3a and Rest as well as NCoR, and it has been suggested that these proteins may be better therapeutic targets than MeCP2.

    “Recently, MeCP2 has been shown to directly interact with Sin3a and Rest as well as NCoR, and it has been suggested that these proteins may be better therapeutic targets than MeCP2 (23).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [23] Cukier, 2008, Genetic modifiers of MeCP2 function in Drosophila, PLoS Genet source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Individuals with these disorders report an increase in anxiety.

    “Although it is not clear whether abnormal developmental expression of NCoR directly impacts these disorders, it is interesting to note that individuals with these disorders report an increase in anxiety (46 -48).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [46] Sansom, 1993, Emotional and behavioural aspects of Rett syndrome., Dev Med Child Neurol source
    • cites [47] Caine, 1983, Psychiatric syndromes in Huntington’s disease., Am J Psychiatry source
    • cites [48] Paulsen, 2001, Neuropsychiatric aspects of Huntington’s disease., J Neurol Neurosurg Psychiatry source

      The Neuropsychiatric Symptom Prevalence section reports anxiety in 51.9% of the Huntington’s disease sample. But the Procedure section says caregivers, not the individuals themselves, reported symptoms, and the paper does not establish an increase in anxiety over time or against a comparison group. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Findingown data

    Estradiol treatment of female rats on the day of birth reduces NCoR mRNA levels in the amygdala to male-like levels.

    “We also report that estradiol treatment in females reduced the levels of NCoR mRNA within the amygdala to male-like levels (P Ͻ 0.01, ANOVA; P Ͻ 0.05, Tukey's post hoc comparison test; Fig. 1D).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Estradiol treatment of female rats on the day of birth reduces NCoR mRNA levels in the medial-basal hypothalamus to male-like levels.

    “We found that females expressed significantly higher levels of NCoR mRNA within the MBH contrasted to males, a confirmation of the sex difference, and that estradiol treatment in females reduced the levels of NCoR mRNA to malelike levels (P Ͻ 0.01, ANOVA; P Ͻ 0.05, Tukey's post hoc comparison test; Fig. 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All animals showed normal juvenile sociability, spending more time in the social chamber than in the nonsocial chamber.

    “All animals showed normal juvenile sociability, spending more time in the social chamber than in the nonsocial chamber.*, P Ͻ 0.05.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Pups in the siRNA experiment were randomly assigned to treatment groups.

    “Litters used in this experiment were combined, and the pups were randomly assigned treatment groups.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Behavioral data were recorded and analyzed by a trained technician blind to all treatments.

    “Each behavior was recorded and then analyzed by a trained technician blind to all treatments using The Observer (Noldus Information Technologies, Leesburg, VA) or Stopwatchϩ (Center for Behavioral Neuroscience, Atlanta, GA) with the exception of the light/dark chamber, which was scored in real time.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NCoR mRNA is ubiquitously distributed in the adult rat brain.

    “Although NCoR mRNA has been found to be ubiquitously distributed (27) in the adult rat brain, we now show that females express higher levels of the corepressor, NCoR, within the MBH and amygdala during development.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Laan, 2005, Neuroanatomical distribution and colocalisation of nuclear receptor corepressor (N-CoR) and silencing mediator of retinoid and thyroid receptors (SMRT) in rat brain., Brain Res source

  • May combine two claims.

    Interpretationreasoning

    Steroid hormone exposure alters the available expression of coregulatory complexes found within a cell and may change the way a cell responds to future hormonal or environmental challenges.

    “Regardless, these data do suggest that steroid hormone exposure alters the available expression of coregulatory complexes found within a cell and may change the way a cell responds to future hormonal or environmental challenges.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Long-term changes in anxiety-like behavior may result from decreased interaction of NCoR with methyl-binding proteins during the neonatal period.

    “Therefore, it is possible that the long-term changes in anxiety-like behavior may result from decreased interaction of NCoR with methyl-binding proteins during the neonatal period.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Coactivators may act to enhance sex differences, and corepressors may act to restrict or lessen the magnitude of some sex differences in males.

    “That is, coactivators may act to enhance sex differences, and corepressors may act to restrict or lessen the magnitude of some sex differences in males.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The period within the first 36 h of neonatal life is critical for sexual differentiation by steroid hormones.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Abnormal cellular distribution of NCoR has been directly linked to Huntington's disease.

    “In addition, abnormal cellular distribution of NCoR has been directly linked to Huntington's disease (26).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Boutell, 1999, Aberrant interactions of transcriptional repressor proteins with the Huntington’s disease gene product, huntingtin., Hum Mol Genet source

  • May combine two claims.

    Interpretationreasoning

    Increased masculinization of social play did not occur in NCoR siRNA-treated females because they are not exposed to the masculinizing actions of the testosterone surge that is occurring in males.

    “it is more likely that increased masculinization of social play did not occur in NCoR siRNA-treated females because they are not exposed to the masculinizing actions of the testosterone surge that is occurring in males.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The testosterone surge occurs in males and has masculinizing actions.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sex differences in anxiety-like behavior are known to occur in adults.

    “Although sex differences in anxiety-like behavior are known to occur in adults (44), we found no sex differences in anxiety-like behavior during the juvenile period.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Johnston, 1991, Sex differences in animal tests of anxiety., Physiol Behav source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Time spent in open and closed arms of the elevated plus maze was recorded by a trained technician blind to treatment groups.

    “Time spent in open and closed arms was later recorded by a trained technician blind to the treatment groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Corepressor complexes cause gene repression through the additional recruitment of HDACs, which deacetylate histones leading to condensation of the chromatin and gene silencing.

    “Corepressor complexes cause gene repression through the additional recruitment of HDACs, which deacetylate histones leading to condensation of the chromatin and gene silencing (45).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Klose, 2006, Genomic DNA methylation: the mark and its mediators., Trends Biochem Sci source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Dissociation curve analysis showed a single peak for all real-time PCR products.

    “After amplification, a dissociation curve analysis was used to ensure purity of the products, a single peak was observed for all products.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Real-time PCR samples were run in duplicate in the same run.

    “Samples were run in duplicate in the same run.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All primers used in the real-time PCR had efficiencies between 93 and 100%.

    “All primers were found to have efficiencies between 93 and 100%.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mutations in the X-linked MECP2 gene, which lead to disruption in MeCP2 protein function, are thought to be the direct cause of Rett syndrome, a progressive neurodevelopmental disorder.

    “For example, mutations in the X-linked MECP2 gene, which lead to disruption in MeCP2 protein function, are thought to be the direct cause of Rett syndrome, a progressive neurodevelopmental disorder (25).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Amir, 1999, Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2., Nat Genet source

  • May combine two claims.

    Study design and conductown data

    NCoR expression levels were not significantly different between control and NCoR siRNA-treated males within the amygdala on PN10, indicating that the effect of the NCoR siRNA infusion is transient.

    “NCoR expression levels were not significantly different between control and NCoR siRNA-treated males within the amygdala on PN10, indicating that the effect of the NCoR siRNA infusion is transient (control siRNA n ϭ 8; NCoR siRNA n ϭ 6).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    A transient decrease in NCoR expression within the developing amygdala leads to an increase in juvenile social play behavior in males and an increase in anxiety-like behavior in both males and females.

    “We find that a transient decrease in NCoR expression within the developing amygdala leads to an increase in juvenile social play behavior in males and an increase in anxietylike behavior in both males and females.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The period within the first 36 h of neonatal life is critical for sexual differentiation by steroid hormones.

  • May combine two claims.

    Study design and conductown data

    NCoR expression levels were not significantly different between control and NCoR siRNA-treated females within the MBH, indicating that the siRNA treatment did not spread from the amygdala.

    “NCoR expression levels were not significantly different between control and NCoR siRNA-treated females within the MBH, indicating that the siRNA treatment did not spread from the amygdala (control siRNA n ϭ 6; NCoR siRNA n ϭ 7).”
    Quote in the paperSubstantial claim
30 of 30

  • The paper relies on this without support.

    Little is known about the role of corepressors such as NCoR on the organization of behavior.

    “Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior.”
    “Although the distribution of NCoR within the rat brain (27) has been reported, little is known about the functional role of NCoR in the developing brain and whether NCoR function has lasting consequences on the formation of typical behavior.”

  • The paper relies on this without support.

    The amygdala is critical in the development of social and anxiety behavior.

    “We then targeted the amygdala with small interfering RNA (siRNA) because it is critical in the development of social and anxiety behavior.”

  • The paper relies on this without support.

    The period within the first 36 h of neonatal life is critical for sexual differentiation by steroid hormones.

    “We chose to disrupt NCoR expression within the first 36 h of neonatal life because this is a time point in which NCoR expression is sexually dimorphic and this period of time is known to be critical for sexual differentiation by steroid hormones.”

  • The paper relies on this without support.

    The testosterone surge occurs in males and has masculinizing actions.

    “it is more likely that increased masculinization of social play did not occur in NCoR siRNA-treated females because they are not exposed to the masculinizing actions of the testosterone surge that is occurring in males.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Reducing the expression of a negative regulator of estrogen receptor alpha during sexual differentiation increases later playfulness of males but has no effect on females.

    “For example, reducing the expression of a negative regulator of estrogen receptor alpha during sexual differentiation actually increases later playfulness of males but has no effect on females (Jessen et al., 2010).”

    From Developmental origins of sex differences in the neural circuitry of play (2020) · cites this paper as Jessen et al., 2010

    The Juvenile social play behavior section reports that reducing NCoR expression in the developing amygdala increased later social play in males but had no observed effect on females. The paper describes NCoR as a corepressor of estrogen receptors, but the passages do not identify estrogen receptor alpha specifically or establish that its regulation caused the play-behavior effect. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Cites

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Cited by

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Related

Authors
Jessen, H. M., Kolodkin, M. H., Bychowski, M. E., Auger, C. J., & Auger, A. P.
Affiliations
University of Wisconsin–Madison (US)
Corresponding author
Auger, Anthony P.
ORCID
Auger, Anthony P.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2010-01-05
Volume
151
Issue
3
Pages
1212-1220
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2009-0594
PMC
PMC2840691
OpenAlex
W2034412497
Semantic Scholar
2315fa42e44be07f2ef2b9fd9e0d7a80ac34afe9
Cited by
53
References
49
Citations by year
2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 4
FWCI
6.73
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
National Institute of Mental Health (R01MH072956)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
nuclear receptor corepressor, NCoR, amygdala development, anxiety-like behavior, sex differences, sexual dimorphism, estradiol, hypothalamus, gene expression regulation, siRNA knockdown, sociability
MeSH terms
Amygdala, Animals, Anxiety, Estradiol, Female, Hypothalamus, Male, Pregnancy, RNA, Messenger, Sex Characteristics, Social Behavior, Rats, Sprague-Dawley, RNA, Small Interfering, Rats, Co-Repressor Proteins

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