Prenatal lipopolysaccharide disrupts maternal behavior, reduces nest odor preference in pups, and induces anxiety: studies of F1 and F2 generations
Abstract
The present study analyzed the transgenerational effects of lipopolysaccharide (LPS; 100 μg/kg) administration on gestational day 18 (GD18) of parental generation on maternal-pups interaction of F1 and F2 generations. Also the long term behavioral effects were observed in male of F2 generation. In F1 generation, the reproductive performance, maternal behavior, maternal aggressive behavior, and general activity in the open field in adulthood were analyzed. In F2 generation, body weight at birth and at weaning, nest odor preference, and general activity in the open field and elevated plus maze in adulthood were assessed. Compared to controls, results showed that in the F1 generation, prenatal LPS exposure (1) increased the latency to full maternal behavior, but all of the females grouped the pups and presented full maternal behavior, (2) reduced the total time boxing and fighting, increased the frequency of retrieving the pups, and increased the number of bites, and (3) did not affect reproductive performance or general activity. In F2 generation, compared with controls, the LPS group exhibited (1) a decrease in body weight at weaning, (2) a decrease in nest odor preference, (3) a decrease in the percentage of time spent in the open arms, a decrease in the percentage of time spent in the center, and an increase in the time spent in the closed arms in the elevated plus maze, and (Huang et al.) no affect behavior in the open field. Prenatal LPS exposure improved maternal care in the F1 generation with regard to nursing and pup survival but did not improve the motivational parameters of maternal behavior likely because of a reduction of maternal stimulation by the pups. In the F2 generation, the reduction of nest odor preference in the pups suggests a less maternal recognition. In adulthood, these rats exhibited increased anxiety-like behavior. These data did not result from motor alterations because rats in both the F1 and F2 generations did not show alterations in open field behavior. This transfer of information across generations likely occurred through nongenetic means because the endotoxin was administered at the end of pregnancy. These results may have implications for clinical therapeutics in human disorders and evolution.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Animal models of systemic prenatal infection induce anxiety-like behavior alterations in offspring.
“These animal models of systemic prenatal infection induce changes in neurobehavioral development consistent with human psychopathology including alterations in offspring anxiety-like behavior (Arsenault et al., 2014; Makinson et al., 2017; Penteado et al., 2014; Schaafsma, W. et al., 2017)”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Penteado et al., 2014
Cites
Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat
Pellow, S., Chopin, P., File, S. E., & Briley, M. (1985) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(85)90031-7 · Cited by 5,822 · see citing works
Deverman, B. E., & Patterson, P. H. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.002 · Cited by 865 · see citing works
Transgenerational induction of defences in animals and plants
Agrawal, A. A., Laforsch, C., & Tollrian, R. (1999) · Nature · doi:10.1038/43425 · Cited by 862 · see citing works
Epigenetic mechanisms and the transgenerational effects of maternal care
Champagne, F. A. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2008.03.003 · Cited by 812 · see citing works
Meyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · see citing works
Reflex-ontogeny and behavioural development of the mouse
Fox, W. M. (1965) · Animal Behaviour · doi:10.1016/0003-3472(65)90041-2 · Cited by 699 · see citing works
Boksa, P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.03.005 · Cited by 603 · see citing works
Cai, Z., Pan, Z.-L., Pang, Y., Evans, O. B., & Rhodes, P. G. (2000) · Pediatric Research · doi:10.1203/00006450-200001000-00013 · Cited by 507 · see citing works
Urakubo, A., Jarskog, L. F., Lieberman, J. A., & Gilmore, J. H. (2001) · Schizophrenia Research · doi:10.1016/s0920-9964(00)00032-3 · Cited by 405 · see citing works
Ashdown, H. F., Dumont, Y., Ng, M., Poole, S., Boksa, P., & Luheshi, G. N. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001748 · Cited by 387 · see citing works
Roth, M. (1961) · BMJ · doi:10.1136/bmj.1.5235.1300 · Cited by 379 · see citing works
Meyer, U., Feldon, J., & Fatemi, S. H. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.05.001 · Cited by 367 · see citing works
Meyer, U., Yee, B. K., & Feldon, J. (2007) · The Neuroscientist · doi:10.1177/1073858406296401 · Cited by 303 · see citing works
THE BEHAVIOR OF THE LABORATORY RAT A Handbook with Tests
Wishaw, I. Q., & Kolb, B. E. (2004) · University of Groningen research database (University of Groningen / Centre for Information Technology) · Cited by 290 · see citing works
Meyer, U., Schwarz, M., & Müller, N. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.06.003 · Cited by 255 · see citing works
Golan, H. M., Lev, V., Hallak, M., Sorokin, Y., & Huleihel, M. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.12.023 · Cited by 253 · see citing works
Brief periods of socialization and later behavior in the rat
Einon, D. F., Morgan, M. J., & Kibbler, C. C. (1978) · Developmental Psychobiology · doi:10.1002/dev.420110305 · Cited by 232 · see citing works
Gayle, D. A., Beloosesky, R., Desai, M., Amidi, F., Nuñez, S., & Ross, M. G. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00664.2003 · Cited by 221 · see citing works
Zhao, B., & Schwartz, J. P. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980401)52:1 · Cited by 208 · see citing works
Maternal behavior deficits in nulliparous oxytocin knockout mice
Pedersen, C. A., Vadlamudi, S. V., Boccia, M. L., & Amico, J. A. (2006) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00162.x · Cited by 190 · see citing works
Parental Care: Evolution, Mechanisms, and Adaptive Significance
(1996) · Advances in the study of behavior · doi:10.1016/s0065-3454(08)x6027-9 · Cited by 185 · see citing works
Nardone, R., Höller, Y., Brigo, F., Seidl, M., Christova, M., Bergmann, J., Golaszewski, S. M., & Trinka, E. (2013) · Brain Research · doi:10.1016/j.brainres.2012.12.034 · Cited by 182 · see citing works
Somatosensation and Maternal Care in Norway Rats
Stern, J. M. (1996) · Advances in the study of behavior · doi:10.1016/s0065-3454(08)60335-6 · Cited by 181 · see citing works
Grindstaff, J. L., Hasselquist, D., Nilsson, J., et al. (2006) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2006.3608 · Cited by 176 · see citing works
Walker, A. K., Nakamura, T., Byrne, R. J., Naicker, S., Tynan, R. J., Hunter, M., & Hodgson, D. M. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.05.010 · Cited by 150 · see citing works
Stress and Anxiety Across the Lifespan: Structural Plasticity and Epigenetic Regulation
Hunter, R. G., & McEwen, B. S. (2013) · Epigenomics · doi:10.2217/epi.13.8 · Cited by 141 · see citing works
Oxytocin antagonism alters rat dams' oral grooming and upright posturing over pups
Pedersen, C. A., & Boccia, M. L. (2003) · Physiology & Behavior · doi:10.1016/j.physbeh.2003.07.011 · Cited by 131 · see citing works
Vuillermot, S., Joodmardi, E., Perlmann, T., Ove Ögren, S., Feldon, J., & Meyer, U. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4831-11.2012 · Cited by 127 · see citing works
Prenatal Lipopolysaccharide Reduces Social Behavior in Male Offspring
Kirsten, T. B., Taricano, M., Maiorka, P. C., Palermo‐Neto, J., & Bernardi, M. M. (2010) · NeuroImmunoModulation · doi:10.1159/000290040 · Cited by 125 · see citing works
Self-citationKirsten, T. B., Chaves‐Kirsten, G. P., Chaible, L. M., Silva, A. C., Martins, D. O., Britto, L. R. G., Dagli, M. L. Z., Torrão, A. S., Palermo‐Neto, J., & Bernardi, M. M. (2012) · Journal of Neuroscience Research · doi:10.1002/jnr.23089 · Cited by 122 · see citing works
Early life immune challenge—effects on behavioural indices of adult rat fear and anxiety
Spencer, S. J., Heida, J. G., & Pittman, Q. J. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.06.032 · Cited by 109 · see citing works
Aisemberg, J., Vercelli, C. A., Bariani, M. V., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056161 · Cited by 104 · see citing works
Xu, D., Chen, Y., Wang, H., Zhao, L., Wang, J., & Wei, W. (2005) · Toxicology Letters · doi:10.1016/j.toxlet.2005.09.009 · Cited by 102 · see citing works
Walker, F. R., March, J., & Hodgson, D. M. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.01.019 · Cited by 96 · see citing works
Eyles, D., Feldon, J., & Meyer, U. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.6 · Cited by 92 · see citing works
Multisensory regulation of maternal behavior and masculine sexual behavior: A revised view
Stern, J. M. (1990) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(05)80219-2 · Cited by 86 · see citing works
Gentsch, C., Lichtsteiner, M., Kräuchi, K., & Feer, H. (1982) · Behavioural Brain Research · doi:10.1016/0166-4328(82)90163-2 · Cited by 84 · see citing works
Some situational and experiential determinants of maternal aggression in mice
Svare, B. B., Betteridge, C., Katz, D., & Samuels, O. B. (1981) · Physiology & Behavior · doi:10.1016/0031-9384(81)90020-2 · Cited by 79 · see citing works
Prenatal lipopolysaccharide reduces motor activity after an immune challenge in adult male offspring
Kirsten, T. B., Taricano, M., Flório, J. C., Palermo‐Neto, J., & Bernardi, M. M. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.03.009 · Cited by 77 · see citing works
Self-citationAvitsur, R., Pollak, Y., & Yirmiya, R. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00927-x · Cited by 73 · see citing works
Walker, A. K., Hawkins, G. E., Sominsky, L., & Hodgson, D. M. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.005 · Cited by 67 · see citing works
Reactive Oxygen Species Contribute to Lipopolysaccharide-Induced Teratogenesis in Mice
Zhao, L., Chen, Y., Wang, H., Ji, Y., Ning, H., Wang, S., Zhang, C., Lu, J.-W., Duan, Z.-H., & Xu, D. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn027 · Cited by 66 · see citing works
[The proinflammatory activity of lipopolysaccharide].
Saluk, J., & Wachowicz, B. (2005) · PubMed · Cited by 64 · see citing works
Paris, J. J., Brunton, P. J., Russell, J. A., & Frye, C. A. (2011) · Stress · doi:10.3109/10253890.2011.628719 · Cited by 60 · see citing works
Curno, O., Behnke, J. M., McElligott, A. G., Reader, T., & Barnard, C. J. (2008) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2008.1612 · Cited by 58 · see citing works
Epigenetic Variations in Heredity and Evolution
Jablonka, E. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.158 · Cited by 57 · see citing works
The Biopsychology of Maternal Behavior in Nonhuman Mammals
Kristal, M. B. (2009) · ILAR Journal · doi:10.1093/ilar.50.1.51 · Cited by 57 · see citing works
Early Effects of Lipopolysaccharide-Induced Inflammation on Foetal Brain Development in Rat
Ghiani, C. A., Mattan, N. S., Nobuta, H., Malvar, J., Boles, J., Ross, M. G., Waschek, J. A., Carpenter, E. M., Fisher, R. S., & de Vellis, J. (2011) · ASN NEURO · doi:10.1042/an20110027 · Cited by 51 · see citing works
Searching for factors underlying cerebral plasticity in the normal and injured brain
Kolb, B. E., Muhammad, A., & Gibb, R. L. (2011) · Journal of Communication Disorders · doi:10.1016/j.jcomdis.2011.04.007 · Cited by 49 · see citing works
Paintlia, M. K., Paintlia, A. S., Singh, A. K., & Singh, I. (2008) · Pediatric Research · doi:10.1203/pdr.0b013e318181e07c · Cited by 49 · see citing works
Walker, F. R., Knott, B., & Hodgson, D. M. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.12.006 · Cited by 49 · see citing works
Bernardi, M. M., Kirsten, T. B., Matsuoka, S. M., Teodorov, E., Habr, S. F., Penteado, S. H. W. N., & Palermo‐Neto, J. (2009) · NeuroImmunoModulation · doi:10.1159/000243085 · Cited by 46 · see citing works
Self-citationGranger, D. A., Hood, K. E., Ikeda, S. C., Reed, C. L., & Block, M. L. (1996) · Brain Behavior and Immunity · doi:10.1006/brbi.1996.0022 · Cited by 46 · see citing works
Neonatal immune challenge does not affect body weight regulation in rats
Spencer, S. J., Mouihate, A., Galic, M. A., Ellis, S. L., & Pittman, Q. J. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00262.2007 · Cited by 45 · see citing works
Effects of Low Dosages of Apomorphine on Maternal Responsiveness in Lactating Rats
Stern, J. M., & Protomastro, M. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00180-5 · Cited by 43 · see citing works
Hood, K. E., Dreschel, N. A., & Granger, D. A. (2002) · Developmental Psychobiology · doi:10.1002/dev.10076 · Cited by 35 · see citing works
Prenatal LPS exposure reduces olfactory perception in neonatal and adult rats
Kirsten, T. B., Chaves, G. P., Taricano, M., Martins, D. O., Flório, J. C., de Britto, L. R. G., Torrão, A. D. S., Palermo‐Neto, J., & Bernardi, M. M. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.049 · Cited by 33 · see citing works
Self-citationCroton zehntneri essential oil: effects on behavioral models related to depression and anxiety
Lazarini, C. A., Uema, A. H., Brandão, G. M., et al. (2000) · Phytomedicine · doi:10.1016/s0944-7113(00)80033-1 · Cited by 33 · see citing works
Interleukin-15 is required for maximal lipopolysaccharide-induced abortion
Lee, A. J., Kandiah, N., Karimi, K., Clark, D. A., & Ashkar, A. A. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.0912442 · Cited by 33 · see citing works
Spontaneous Miscarriages Are Explained by the Stress/Glucocorticoid/Lipoxin A4 Axis
Xu, Z., Zhao, J., Zhang, H., Tang, K., Xu, P., Cai, W., Katirai, F., Ye, D., Huang, Y., & Huang, B. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202807 · Cited by 32 · see citing works
Kirsten, T. B., de Oliveira, B. P. S., de Oliveira, A. P. L., Kieling, K., de Lima, W. T., Palermo‐Neto, J., & Bernardi, M. M. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.04.023 · Cited by 31 · see citing works
Self-citationInflammatory Agents Involved in Septic Miscarriage
Aisemberg, J., Vercelli, C. A., Wolfson, M. L., et al. (2010) · NeuroImmunoModulation · doi:10.1159/000258710 · Cited by 30 · see citing works
Levine, J. B., Leeder, A., Parekkadan, B., Berdichevsky, Y., Rauch, S. L., Smoller, J. W., Konradi, C. L., Francois Berthiaume, B., & Yarmush, M. L. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.014 · Cited by 30 · see citing works
Soto, A. M. S., Kirsten, T. B., Reis-Silva, T. M., Martins, M. D. F. M., Teodorov, E., Flório, J. C., Palermo‐Neto, J., Bernardi, M. M., & Bondan, E. F. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.03.003 · Cited by 25 · see citing works
Self-citationIndividual differences in glucose homeostasis: Do our early life interactions with bacteria matter?
Walker, F. R., Owens, J. A., Ali, S. O., & Hodgson, D. M. (2006) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2005.11.004 · Cited by 24 · see citing works
Perinatal Periodontal Disease Reduces Social Behavior in Male Offspring
Pimentel, S. P., Casati, M. Z., Cirano, F. R., Ribeiro, F. V., Casarin, R. V., Kirsten, T. B., Chaves-Kirsten, G. P., Duarte, P., & Bernardi, M. M. (2012) · NeuroImmunoModulation · doi:10.1159/000342987 · Cited by 9 · see citing works
Self-citationPenteado, S. H. W. N., Massoco, C. D. O., Kirsten, T. B., Reis-Silva, T. M., de Melo, R. C., Acenjo, M. K., Queiroz‐Hazarbassanov, N., & Bernardi, M. M. (2013) · Psychology & Neuroscience · doi:10.3922/j.psns.2013.1.06 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Neuroinflammation as a risk factor for attention deficit hyperactivity disorder
Dunn, G. A., Nigg, J. T., & Sullivan, E. L. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.05.005 · Cited by 299 · see citing works
Makinson, R., Lloyd, K., Rayasam, A., McKee, S., Brown, A., Barila, G., Grissom, N., George, R., Marini, M., Fabry, Z., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.07.016 · Cited by 67 · see citing works
Sex Differences in Neurodevelopmental Disorders: A Key Role for the Immune System
Breach, M. R., & Lenz, K. M. (2022) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2022_308 · Cited by 62 · see citing works
- Authors
- Penteado, S. H. W., Teodorov, E., Kirsten, T. B., Eluf, B. P., Reis-Silva, T. M., Acenjo, M. K., de Melo, R. C., Suffredini, I. B., & Bernardi, M. M.
- Affiliations
- Universidade Paulista (BR)
- Universidade Federal do ABC (BR)
- Universidade de São Paulo (BR)
- Corresponding author
- Bernardi, Maria M.
- ORCID
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 738
- Pages
- 342-351
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W1977047155
- Cited by
- 33
- References
- 67
- Citations by year
- 2025: 2 · 2024: 9 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 4 · 2015: 2
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CNPq ( PIBIC), FAPESP Thematic Award (09/51886-3)
- UNIP (7-02-747/2010, 7-02-839/2012)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- lipopolysaccharide, maternal behavior, transgenerational effects, maternal recognition, anxiety-like behavior, maternal aggression, pup retrieval, maternal care, developmental programming
- MeSH terms
- Aggression, Animals, Anxiety, Behavior, Animal, Birth Weight, Female, Lactation, Lipopolysaccharides, Male, Maternal Behavior, Odorants, Pregnancy, Prenatal Exposure Delayed Effects, Reproduction, Weaning, Maze Learning, Maternal Exposure, Rats
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review