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Cited by 53Effects and risks of endocrine disrupting chemicalsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

Open access
Liu, Zhi-Hua, Ding, Jin-Jun, Yang, Qian-Qian, Song, Hua-Zeng, Chen, Xiang-Tao, Xu, Yi, Xiao, Gui-Ran, Wang, Hui-Li·2016·Scientific Reports
DOI 10.1038/srep32492PMC PMC5006158
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Abstract

Bisphenol-A (BPA, 4, 4′-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABA A Rβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABA A Rβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

AI snapshot

Written from the paper’s full text.

TL;DR

Chronic early developmental bisphenol-A (BPA) exposure impaired spatial memory in both male and female Sprague-Dawley rats without a sex-specific effect. The impairment was accompanied by reduced hippocampal dendritic complexity, spine density, mushroom-shaped spines, and Arc expression, plus increased inhibitory synaptic strength and postsynaptic GABAARβ2/3 in cultured CA1 neurons.

Key findings

  • In the Morris water maze, BPA treatment significantly affected probe-trial time in the target quadrant (F(2, 35) = 3.837, p = 0.033) and platform crossings (F(2, 35) = 6.561, p = 0.004), with no significant sex × BPA interaction (p = 0.711; p = 0.910) or sex main effect (p = 0.354; p = 0.669).
  • BPA reduced dendritic complexity in hippocampal CA1 and dentate gyrus (DG), and decreased dendritic spine density: in CA1, males showed 15.60% and 19.35% decreases and females 9.54% and 28.12% decreases at 0.15 and 7.50 mg/kg/day, respectively; in DG, males showed 19.11% and 25.70% decreases and females 10.52% and 12.25% decreases.
  • The percentage of mushroom-shaped spines decreased in CA1 by 29.69% and 33.50% in males and 41.68% and 39.65% in females, and in DG by 29.66% and 34.36% in males and 41.81% and 45.39% in females, at the two BPA doses.
  • Arc expression decreased in CA1 only at 7.50 mg/kg/day in both sexes (males 0.56 ± 0.06, females 0.54 ± 0.07, p < 0.001) and in DG at both doses (males 0.73 ± 0.06 and 0.66 ± 0.04; females 0.81 ± 0.03 and 0.65 ± 0.05). Acute BPA increased mIPSC amplitude (35.85 ± 1.87 pA to 50.94 ± 3.48 pA, p < 0.001) without changing mIPSC frequency, and increased surface GABAARβ2/3 puncta intensity (0.91 ± 0.02 to 1.12 ± 0.08), while mEPSC amplitude/frequency and VGAT puncta were unchanged.

Methods

  • Sprague-Dawley pups were exposed to BPA indirectly through maternal milk during lactation and then directly after weaning via drinking water at 0, 0.15, or 7.50 mg/kg/day; Morris water maze testing occurred at 12 weeks of age.
  • Hippocampal morphology was assessed by Golgi-Cox staining, Arc protein by Western blotting, and synaptic transmission/immunocytochemistry in primary hippocampal cultures exposed to BPA for 2 hrs at 14 days in vitro.
  • Statistical analysis used one-way, two-way, or three-way repeated ANOVA as appropriate, followed by Fisher’s protected least significant difference (PLSD) with p < 0.05 considered significant.

Limitations

  • The paper does not include a formal limitations section. It states that offspring were exposed indirectly in utero and through maternal milk, and notes the possibility that BPA may affect offspring memory by modifying maternal behavior or via maternal stress.
  • Evident from the text: the sex-independent conclusion is based on two BPA doses in one rat strain and age, and the synaptic mechanism was tested after acute 2-hr BPA exposure in cultured neurons rather than after chronic in vivo exposure, so the link between the in vitro synaptic findings and in vivo memory deficits is inferential.
  • Evident from the text: the study reports associations between Arc/GABAAR changes and memory impairment but does not include direct causal manipulations of Arc or GABAARβ2/3.

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

Integrity signals

Registry

Crossref · 10.1038/srep32492

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

6 tests recomputed · 0 with the reported and recomputed p on opposite sides of .05

Claims the paper makes

10 of 35 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Damage of any part of the hippocampal circuit affects learning and memory.

    “Damage of any part of this circuit will affect the process of learning and memory30313233.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [30] Hiroo, O. et al. Neurotoxic damage of granule cells in the dentate gyrus and the cerebellum and cognitive deficit following neonatal administration of phenytoin in mice. Journal of Neuropathology & Experimental Neurology. 61, 956–967 (2002). source
    • cites [31] Spanswick, S. C., J. R. Epp, J. R. Keith & R. J. Sutherland . Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial memory deficits that are not reversed by chronic treatment with corticosterone or fluoxetine. Hippocampus. 17, 137–146 (2007). source

      The Discussion (page unavailable) says dentate gyrus integrity is critical for spatial learning in rats and reports impaired spatial-learning performance after selective damage. It does not establish that damage to any part of the hippocampal circuit affects learning and memory generally. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [32] Conrad, C. D. & E. J. Roy . Dentate gyrus destruction and spatial learning impairment after corticosteroid removal in young and middle-aged rats. Hippocampus. 5, 1–15 (1995). source
  • Premisecitation

    Detectable levels of BPA have been found in human and animal fluids such as urine, blood, and breast milk.

    “detectable levels of BPA have been found in fluids of human and animals, such as urine24, blood25 and breast milk26.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [24] Calafat, A. M. et al. Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect. 113, 391–395 (2005). source
    • cites [25] Ikezuki, Y., O. Tsutsumi, Y. Takai, Y. Kamei & Y. Taketani . Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod. 17, 2839–2841 (2002). source
    • cites [26] Kuruto-Niwa, R., Y. Tateoka, Y. Usuki & R. Nozawa. Measurement of bisphenol A concentrations in human colostrum. Chemosphere. 66, 1160–1164 (2007). source
  • Findingown data

    BPA exposure did not change integrated puncta intensity of excitatory synaptic markers VGlut1 and PSD95 in cultured hippocampal neurons.

    “integrated puncta intensity of the excitatory synaptic markers, vesicular glutamate transporter 1 (VGlut1), a presynaptic excitatory marker (Fig. 7B, Control, 1.00 ± 0.050; BPA, 1.10 ± 0.04) and PSD95, a postsynaptic excitatory marker (Fig. 7B, Control, 1.00 ± 0.05; BPA, 0.84 ± 0.05), had no significant changes after BPA exposure.”
    Quote in the paperSubstantial claim
  • Findingown data

    BPA exposure at 7.50 mg/kg/day decreased Arc expression in hippocampal CA1 region in both male and female rats.

    “In CA1 region, Arc decreased dramatically only after 7.50 mg/kg/day BPA exposure in both male (Fig. 5B, Control, 1.00 ± 0.00; BPA 0.15 mg/kg/day, 1.00 ± 0.01, p > 0.05; BPA 7.50 mg/kg/day, 0.56 ± 0.06, p < 0.001) and female rats (Fig. 5B, Control, 1.00 ± 0.00; BPA 0.15 mg/kg/day, 1.01 ± 0.03, p > 0.05; BPA 7.50 mg/kg/day, 0.54 ± 0.07, p < 0.001).”
    • Also stated in: § Discussion · plain
      “Arc expression decreased significantly only upon high dose of BPA exposure in CA1 region”
    Quote in the paperSubstantial claim
  • Findingown data

    BPA exposure decreased dendritic complexity in hippocampal CA1 and DG neurons of male and female rats.

    “BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons.”
    • Also stated in: § BPA decreased dendritic complexity · hedged
      “These results indicated that BPA exposure negatively affected dendritic formation and development.”
    • Also stated in: § Discussion · plain
      “Golgi-cox staining experiments revealed that dendritic complexity was impaired upon BPA exposure, manifested as reduced dendrite number at different branch order and decreased dendritic crossings in CA1 and DG regions.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 8
  • The quote only partly states this claim. 2

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

    Premisecitation

    α4-GABAAR KO mice exhibited enhanced trace and contextual fear conditioning, along with enhancement of hippocampus-dependent learning and memory.

    “α4-GABAAR knock out (KO) mice exhibited enhanced trace and contextual fear conditioning, along with an enhancement of hippocampus-dependent learning and memory50.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [50] Cushman, J. D., M. D. Moore, R. W. Olsen & M. S. Fanselow . The role of the delta GABA(A) receptor in ovarian cycle-linked changes in hippocampus-dependent learning and memory. Neurochem Res. 39, 1140–1146 (2014). source

      The Introduction (p. 3) attributes enhanced trace fear conditioning and hippocampus-dependent learning to female δ-GABAAR knockout mice, not α4-GABAAR knockout mice. The contextual-fear results (p. 6) likewise report enhancement in δ-GABAAR knockout mice. The cited paper therefore identifies a different receptor subunit from the one in the claim. (LLM, conf=0.89)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

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

    Premisecitation

    Inhibition of α5 GABAAR attenuated memory deficits induced by inflammation.

    “Inhibition of α5 GABAAR attenuated the memory deficits induced by inflammation51.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [51] Wang, D.-S. et al. Memory Deficits Induced by Inflammation Are Regulated by α5-Subunit-Containing GABAA Receptors. Cell Reports. 2, 488–496 (2012). source

  • Classified as probably not a substantial claim.

    Premisecitation

    Global or local deletion of Arc in the hippocampus impairs spatial learning consolidation.

    “global or local deletion of Arc in the hippocampus has been demonstrated to impair the spatial learning consolidation3940.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [39] Plath, N. et al. Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron. 52, 437–444 (2006). source
    • cites [40] JF, G. et al. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. Journal of Neuroscience the Official Journal of the Society for Neuroscience. 20, 3993–4001 (2000). source

      The section on intrahippocampal Arc antisense infusions and the Discussion report impaired consolidation of spatial water-task memory in rats after local inhibition of Arc expression. The paper does not demonstrate global Arc deletion, and its local intervention was antisense-mediated inhibition rather than deletion. Page numbers are unavailable in our copy. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Dendritic spine morphology and number are highly dynamic and variable, and correlated with memory formation.

    “Dendritic spine morphology and number are highly dynamic and variable56, which were reported to be correlated with memory formation.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [5] Harris, K. M., J. C. Fiala & L. Ostroff . Structural changes at dendritic spine synapses during long-term potentiation. Philos T Roy Soc B. 358, 745–748 (2003). source

      Section 1, “No Spine Splitting,” links proposed changes in spine size or number to cellular mechanisms of learning and memory. The paper also reports spine outgrowth and synapse enlargement during LTP, but it does not establish that spine morphology and number are generally highly dynamic or demonstrate a correlation with memory formation. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [6] Bosch, M. et al. Structural and Molecular Remodeling of Dendritic Spine Substructures during Long-Term Potentiation. Neuron. 82, 444–459 (2014). source

      The Introduction (page unavailable) says spines enlarge during long-term potentiation and shrink during long-term depression, supporting dynamic morphology. It also describes synaptic structural change as a basis of learning and memory, but does not establish a correlation between spine number and memory formation or show that spine number is highly dynamic. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Arc blockade impairs LTP maintenance and hippocampal-dependent spatial learning.

    “Arc blockade impairs long term potentiation (LTP) maintenance and hippocampal-dependent spatial learning15.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [15] Guzowski, J. F. et al. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J Neurosci. 20, 3993–4001 (2000). source

      The paper reports that inhibiting Arc protein expression impaired LTP maintenance and long-term memory consolidation for a spatial water task. It explicitly says task acquisition was unaffected, so describing the effect as impaired spatial learning overstates the finding. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Adult-born neurons can influence hippocampus-dependent learning and memory.

    “These adult-born neurons can influence certain forms of hippocampus-dependent learning and memory formation3536.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [35] Garthe, A., J. Behr & G. Kempermann . Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLos One. 4, 7 (2009). source
    • cites [36] Deng, W., M. D. Saxe, I. S. Gallina & F. H. Gage . Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J Neurosci. 29, 13532–13542 (2009). source

  • May combine two claims.

    Findingown data

    Acute BPA exposure (2 hrs) increased mIPSC amplitude in cultured hippocampal CA1 neurons without affecting mIPSC frequency.

    “BPA treatment (2 hrs) in cultured hippocampal neurons led to a robust increase in mIPSC amplitude (Fig. 6B, Control, 35.85 ± 1.87 pA; BPA, 50.94 ± 3.48 pA, p < 0.001) without affecting the mIPSC frequency (Fig. 6B, Control, 0.65 ± 0.11 Hz; BPA, 0.96 ± 0.11 Hz), which indicated that acute BPA exposure enhanced inhibitory synaptic transmission.”
    • Also stated in: § Abstract · plain
      “BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency”
    • Also stated in: § Discussion · plain
      “we found that BPA enhanced inhibitory synaptic strength”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    BPA exposure decreased dendritic spine density in hippocampal CA1 and DG in a dose-dependent manner in male and female rats.

    “Dendritic spine density in hippocampal CA1 and DG decreased significantly in a dose-dependent manner, with males exhibiting 15.60% (BPA 0.15 mg/kg/day, p < 0.01) and 19.35% (BPA 7.50 mg/kg/day, p < 0.001) decrease in CA1, respectively.”
    • Also stated in: § Discussion · plain
      “we observed decreased dendritic spine density, altered spine morphology, along with reduced Arc expression in hippocampal CA1 and DG regions.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    BPA exposure reduced the percentage of mushroom shaped spines in hippocampal CA1 and DG neurons in male and female rats.

    “We discovered that the percentage of mushroom shaped spines reduced significantly as a result of BPA exposure.”
    • Also stated in: § BPA altered dendritic spine density and morphology · plain
      “the percentage of mushroom shaped spines in CA1 neurons decreased by 29.69% and 33.50% in male rats and 41.68%, 39.65% in female rats upon 0.15 mg/kg/day and 7.50 mg/kg/day BPA exposure, respectively (Fig. 4C).”
    • Also stated in: § BPA altered dendritic spine density and morphology · plain
      “In DG, the percentage decreased by 29.66%, 34.36% and 41.81%, 45.39% in male and female rats, respectively (Fig. 4C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    BPA-induced spatial memory deficits were sex-independent, with no significant sex × BPA interaction or main effect of sex.

    “Strikingly, we found that BPA induced spatial memory deficits were sex-independent.”
    • Also stated in: § BPA impaired spatial memory in SD male and female rats · plain
      “No significant changes were observed following interaction of sex × BPA treatment (F(2, 33) = 0.346, p = 0.711; F(2, 33) = 0.094, p = 0.910, respectively) or main factor of sex (F(1, 35) = 0.888, p = 0.354; F(1, 35) = 0.187, p = 0.669, respectively) (Fig. 2G,H).”
    • Also stated in: § Discussion · plain
      “the MWM results revealed that BPA impaired spatial memory in a sex-independent manner.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    BPA impaired dendritic spine formation and maturation, which may contribute to impaired spatial memory.

    “These results suggested that BPA impaired dendritic spine formation and maturation, which may contribute to the impaired spatial memory caused by BPA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    BPA has been demonstrated to be associated with alteration in sexual dimorphisms of the CNS and behavioral impairment in rats.

    “BPA has been demonstrated to be associated with alteration in sexual dimorphisms of the central nervous system (CNS) and behavioral impairment in rats1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] Kubo, K. et al. Exposure to bisphenol A during the fetal and suckling periods disrupts sexual differentiation of the locus coeruleus and of behavior in the rat. Neurosci Lett. 304, 73–76 (2001). source

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

    Premisecitation

    Dendritic development is regulated by a combination of intrinsic programs and extrinsic factors.

    “Dendritic development is regulated by a combination of intrinsic programs and extrinsic factors78.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Cline, H. T. Dendritic arbor development and synaptogenesis. Current Opinion in Neurobiology. 11, 118–126 (2001). source
    • cites [8] Miller, F. D. & D. R. Kaplan . Signaling mechanisms underlying dendrite formation. Current Opinion in Neurobiology. 13, 391–398 (2003). source

  • Classified as probably not a substantial claim.

    Premisecitation

    Morphological alterations of dendritic spines have profound effects on efficacy of synaptic transmission.

    “Morphological alterations of dendritic spines have been shown to have profound effects on the efficacy of synaptic transmission43.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Fischer, M., S. Kaech, D. Knutti & A. Matus . Rapid actin-based plasticity in dendritic spines. Neuron. 20, 847–854 (1998). source

  • Classified as probably not a substantial claim.

    Premisecitation

    Functional strength of GABAergic synapses changes in proportion with the number of postsynaptic GABAARs.

    “the functional strength of GABAergic synapses changes in proportion with the number of postsynaptic GABAARs4546.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [45] Otis, T. S., Y. De, Koninck & I. Mody . Lasting potentiation of inhibition is associated with an increased number of gamma-aminobutyric acid type A receptors activated during miniature inhibitory postsynaptic currents. Proceedings of the National Academy of Sciences. 91, 7698–7702 (1994). source
    • cites [46] Nusser, Z., S. Cull-Candy & M. Farrant . Differences in synaptic GABA(A) receptor number underlie variation in GABA mini amplitude. Neuron. 19, 697–709 (1997). source

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

    Premisecitation

    Arc regulates spine size and the distribution of spine type.

    “It has been demonstrated that Arc regulates spine size and the distribution of spine type14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Peebles, C. L. et al. Arc regulates spine morphology and maintains network stability in vivo . P Natl Acad Sci USA. 107, 18173–18178 (2010). source

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

    Premisecitation

    The mushroom shaped spine is relatively stable and mature among the four types of spines.

    “The mushroom shaped spine is relatively stable and mature among the four types of spines1617.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Bourne, J. & K. M. Harris. Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol. 17, 381–386 (2007). source
    • cites [17] Nimchinsky, E. A., B. L. Sabatini & K. Svoboda . Structure and function of dendritic spines. Annu Rev Physiol. 64, 313–353 (2002). source

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

    Premisecitation

    High-dose BPA exposure to pregnant mice affects hippocampal neurogenesis and memory retention in the second generation.

    “It has been reported that high-dose BPA exposure to pregnant mice affects hippocampal neurogenesis and memory retention in the second generation, which have no experience of BPA exposure27.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Jang, Y. J. et al. High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations. Toxicology. 296, 73–82 (2012). source

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

    Premisecitation

    BPA may negatively affect neurogenesis in DG.

    “BPA may negatively affect neurogenesis in DG3441”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Tiwari, S. K., S. Agarwal, A. Tripathi & R. K. Chaturvedi . Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway. Mol Neurobiol. 12, 12 (2015). source
    • cites [41] Kim, M. E. et al. Exposure to bisphenol A appears to impair hippocampal neurogenesis and spatial learning and memory. Food Chem Toxicol. 49, 3383–3389 (2011). source

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

    Premisecitation

    Arc is highly expressed in dendrites, post-synaptic density, and nucleus.

    “Arc (also known as Arg3.1), an activity-regulated cytoskeleton-associated protein which belongs to the immediate early gene family, is highly expressed in dendrites910, post-synaptic density (PSD)1112, and nucleus13.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] Rodriguez, J. J. et al. Long-term potentiation in the rat dentate gyrus is associated with enhanced Arc/Arg3.1 protein expression in spines, dendrites and glia. Eur J Neurosci. 21, 2384–2396 (2005). source
    • cites [11] Moga, D. E., M. A. Calhoun, P. Worley, J. H. Morrison & M. L. Shapiro . Activity-regulated cytoskeletal-associated protein is localized to recently activated excitatory synapses. Neuroscience. 125, 7–11 (2004). source
    • cites [13] Bloomer, W. A., H. M. VanDongen & A. M. VanDongen. Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies. Brain Res. 11, 20–33 (2007). source

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

    Premisecitation

    BPA declined neurogenesis in DG.

    “Another reason for BPA induced spatial memory deficits may be that BPA declined neurogenesis in DG2734.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Jang, Y. J. et al. High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations. Toxicology. 296, 73–82 (2012). source
    • cites [34] Tiwari, S. K., S. Agarwal, A. Tripathi & R. K. Chaturvedi . Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway. Mol Neurobiol. 12, 12 (2015). source
21 of 21

  • The paper relies on this without support.

    Acute BPA exposure in cultured hippocampal CA1 neurons is a valid model for the chronic developmental BPA exposure effects on hippocampal synaptic transmission in vivo.

    “Neurons were exposed to BPA for 2 hrs on 14 day in vitro (DIV).”
    “we next explored whether the synaptic transmission was affected upon BPA exposure in cultured hippocampal CA1 neurons.”

  • The paper relies on this without support.

    BPA's effects on offspring spatial memory are not mediated by altered maternal behavior.

    “the offspring used in this study were indirectly exposed to BPA from in-utero environment and maternal milk during early development”
    “the result indicated a possibility that BPA may affect the offspring memory by modifying their mother’s behavior.”
2 of 2

Statistics that don’t add up

Each reported p-value recomputed from its test statistic and degrees of freedom.

  • Inconsistent p-value: F(1, 35) = 0.888, p = .354

    Minor

    The paper reports p = .354 here; recomputing from the test statistic and its degrees of freedom gives p = .352. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .354 · recomputed p = .352

  • Inconsistent p-value: F(2, 35) = 3.837, p = .033

    Minor

    The paper reports p = .033 here; recomputing from the test statistic and its degrees of freedom gives p = .031. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .033 · recomputed p = .031

  • Inconsistent p-value: F(2, 33) = 0.346, p = .711

    Minor

    The paper reports p = .711 here; recomputing from the test statistic and its degrees of freedom gives p = .710. The check cannot tell whether the statistic or the p-value is the misprint.

    Reported p = .711 · recomputed p = .710

3 of 3

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Doesn’t add upF(2, 35) = 3.837reported p = .033 · recomputed p = .031

    “F(2, 35) = 3.837, p = .033”

  • Doesn’t add upF(2, 33) = 0.346reported p = .711 · recomputed p = .710

    “F(2, 33) = 0.346, p = .711”

  • Doesn’t add upF(1, 35) = 0.888reported p = .354 · recomputed p = .352

    “F(1, 35) = 0.888, p = .354”

  • Not confirmedF(1, 35) = 0.187reported p = .669 · recomputed p = .668

    “F(1, 35) = 0.187, p = .669”

  • ConsistentF(2, 35) = 6.561reported p = .004 · recomputed p = .004

    “F(2, 35) = 6.561, p = .004”

  • ConsistentF(2, 33) = 0.094reported p = .91 · recomputed p = .911

    “F(2, 33) = 0.094, p = .910”

6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Probe-trial ANOVA uses inconsistent denominator degrees of freedom

    Minor

    For each probe-trial outcome, the reported treatment, sex, and sex × treatment tests come from the same two-way ANOVA, but the interaction uses 33 denominator degrees of freedom while the main effects use 35.

1 of 1

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1371/journal.pone.0110482

    Info

    The cited work was retracted on 2019-07-18 (notice 10.1371/journal.pone.0220212), not before this paper was published (2016-08-31).

    Cited work 10.1371/journal.pone.0110482 · retracted 2019-07-18 · notice 10.1371/journal.pone.0220212 · this paper published 2016-08-31

1 of 1

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. JF, G. et al. Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. Journal of Neuroscience the Official Journal of the Society for Neuroscience. 20, 3993–4001 (2000). · DOI · Paper page

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Authors
Liu, Z.-H., Ding, J.-J., Yang, Q.-Q., Song, H.-Z., Chen, X.-T., Xu, Y., Xiao, G.-R., & Wang, H.-L.
Affiliations
  • Hefei University of Technology (CN)
  • Anhui Medical University (CN)
Corresponding author
Wang, Hui-Li
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-08-31
Volume
6
Issue
1
Pages
32492-32492
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep32492
PMC
PMC5006158
OpenAlex
W2508103045
Semantic Scholar
68cee091828ba1e2f826ddcef7da983c076af916
Cited by
53
References
53
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 11 · 2022: 8 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 8 · 2017: 3
FWCI
3.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (973 Program, 31200851, 21477031, 31401671)
  • Anhui University
  • Anhui University of Chinese Medicine (2015sbgj005)
  • Hefei University
  • Hefei University of Technology
  • Program for New Century Excellent Talents in University (NCET-12-0835)
  • National Key Research and Development Program of China (2012CB525003)
  • Specialized Research Fund for the Doctoral Program of Higher Education of China (20130111110024)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
bisphenol A, endocrine disruptors, spatial memory, hippocampus, dendritic spine morphology, dendritic complexity, Arc expression, miniature inhibitory postsynaptic currents, CA1 neurons, dentate gyrus, sex differences, developmental neurotoxicity, xenoestrogens
MeSH terms
Bisphenol A Compounds, Administration, Oral, Air Pollutants, Occupational, Animals, Animals, Newborn, Benzhydryl Compounds, Cytoskeletal Proteins, Female, Gene Expression Regulation, Male, Nerve Tissue Proteins, Synaptic Transmission, Neuronal Plasticity, Phenols, Receptors, GABA-A, Synapses, Temporal Lobe, Rats, Sprague-Dawley, Pyramidal Cells, Dentate Gyrus, Dendritic Spines, Rats, Synaptic Potentials, CA1 Region, Hippocampal, Primary Cell Culture, Spatial Memory

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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