Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy
Abstract
Intrauterine inflammation is a major risk for offspring neurodevelopmental brain damage and may result in cognitive limitations and poor cognitive and perceptual outcomes. Pro-inflammatory cytokines, stimulated during inflammatory response, have a pleotrophic effect on neurons and glia cells. They act in a dose-dependent manner, activate cell-death pathways and also act as trophic factors. In the present study, we have examined in mice the effect of short, systemic maternal inflammation on fetal brain development. Maternal inflammation, induced by lipopolysaccharide (LPS) at gestation day 17, did not affect morphogenic parameters and reflex development during the first month of life. However, maternal inflammation specifically increased the number of pyramidal and granular cells in the hippocampus, as well as the shrinkage of pyramidal cells, but not of the granular cells. No additional major morphological differences were observed in the cerebral cortex or cerebellum. In accordance with the morphological effects, maternal inflammation specifically impaired distinct forms of learning and memory, but not motor function or exploration in the adult offspring. The specific deficiency observed, following maternal inflammation, may suggest particular sensitivity of the hippocampus and other associated brain regions to inflammatory factors during late embryonic development.
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Prenatal LPS treatment impaired learning to associate a cue with the platform in the Morris water maze.
“learning to associate a cue with the platform in the Morris-water maze (Golan et al., 2005)”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Golan et al., 2005
Cites
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340 · see citing works
Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.274 · Cited by 3,292 · see citing works
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
Phillips, R. G., & LeDoux, J. E. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.274 · Cited by 3,262 · see citing works
Functional neurogenesis in the adult hippocampus
van Praag, H., Schinder, A. F., Christie, B. R., Toni, N., Palmer, T. D., & Gage, F. H. (2002) · Nature · doi:10.1038/4151030a · Cited by 2,853 · see citing works
Dinarello, C. A. (2000) · CHEST Journal · doi:10.1378/chest.118.2.503 · Cited by 2,047 · see citing works
Applications of the Morris water maze in the study of learning and memory
D’Hooge, R., & Deyn, P. P. D. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00067-4 · Cited by 2,035 · see citing works
Gould, E., Tanapat, P., McEwen, B. S., Flügge, G., & Fuchs, E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.3168 · Cited by 1,395 · see citing works
Control of Synaptic Strength by Glial TNFα
Beattie, E. C., Stellwagen, D., Morishita, W., Bresnahan, J. C., Ha, B. K., Von Zastrow, M., Beattie, M. S., & Malenka, R. C. (2002) · Science · doi:10.1126/science.1067859 · Cited by 1,344 · see citing works
Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair
Sofroniew, M. V., Howe, C. L., & Mobley, W. C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1217 · Cited by 1,284 · see citing works
Cytokines and the nervous system II: actions and mechanisms of action
Rothwell, N. J., & Hopkins, S. J. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93890-a · Cited by 922 · see citing works
(2000) · Cited by 919 · see citing works
Bayer, S. A. (1980) · The Journal of Comparative Neurology · doi:10.1002/cne.901900107 · Cited by 913 · see citing works
Sutherland, R. J., Whishaw, I. Q., & Kolb, B. (1983) · Behavioural Brain Research · doi:10.1016/0166-4328(83)90188-2 · Cited by 592 · 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
A neuromodulatory role of interleukin-1β in the hippocampus
Schneider, H., Pitossi, F., Balschun, D., Wagner, A., del Rey, A., & Besedovsky, H. O. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7778 · Cited by 498 · see citing works
Malleret, G., Haditsch, U., Genoux, D., Jones, M. W., Bliss, T. V. P., Vanhoose, A. M., Weitlauf, C., Kandel, E. R., Winder, D. G., & Mansuy, I. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00264-1 · Cited by 470 · see citing works
Cunningham, A. J., Murray, C. A., O'Neill, L. A. J., Lynch, M. A., & O'Connor, J. J. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(95)12252-4 · Cited by 433 · see citing works
Ader, R., Weijnen, J. A. W. M., & Moleman, P. (1972) · Psychonomic Science · doi:10.3758/bf03335453 · Cited by 432 · see citing works
Bayer, S. A. (1980) · The Journal of Comparative Neurology · doi:10.1002/cne.901900108 · Cited by 381 · see citing works
Tumor necrosis factor alters synaptic transmission in rat hippocampal slices.
Tancredi, V., D'Arcangelo, G., Grassi, F., Tarroni, P., Palmieri, G., Santoni, A., & Eusebi, F. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90071-e · Cited by 326 · see citing works
Neumann, H., Schweigreiter, R., Yamashita, T., Rosenkranz, K., Wekerle, H., & Barde, Y. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-00854.2002 · Cited by 323 · see citing works
Tyzio, R., Represa, A., Jorquera, I., Ben-Ari, Y., Gozlan, H., & Aniksztejn, L. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-23-10372.1999 · Cited by 297 · see citing works
BDNF Blocks Caspase-3 Activation in Neonatal Hypoxia–Ischemia
Han, B. H., D'Costa, A. P., Back, S. A., Parsadanian, M., Patel, S., Shah, A. R., Gidday, J. M., Srinivasan, A. N., Deshmukh, M., & Holtzman, D. M. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0275 · Cited by 267 · see citing works
Yang, L., Lindholm, K., Konishi, Y., Li, R., & Shen, Y. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03025.2002 · Cited by 255 · see citing works
Dammann, O., Kuban, K., & Leviton, A. (2002) · Mental Retardation and Developmental Disabilities Research Reviews · doi:10.1002/mrdd.10005 · Cited by 250 · see citing works
Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice
Fidel, P. L., Romero, R. J., Wolf, N. A., Cutright, J. L., Ramírez, M., Araneda, H., & Cotton, D. B. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(94)70180-6 · Cited by 249 · see citing works
Tancredi, V., D’Antuono, M., Café, C., Giovedı̀, S., Buè, M. C., D’Arcangelo, G., Onofri, F., & Benfenati, F. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750634.x · Cited by 249 · see citing works
Further studies of hippocampal representation during odor discrimination learning.
Eichenbaum, H., Mathews, P., & Cohen, N. J. (1989) · Behavioral Neuroscience · doi:10.1037//0735-7044.103.6.1207 · Cited by 230 · see citing works
Involvement of Tumor Necrosis Factor Alpha in Hippocampal Development and Function
Golan, H. M. (2003) · Cerebral Cortex · doi:10.1093/cercor/bhg108 · Cited by 204 · see citing works
Self-citationAltman, J., & Bayer, S. A. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903010303 · Cited by 198 · see citing works
Cheng, Y. D., Gidday, J. M., Yan, Q., Shah, A. R., & Holtzman, D. M. (1997) · Annals of Neurology · doi:10.1002/ana.410410416 · Cited by 185 · see citing works
Further studies of hippocampal representation during odor discrimination learning.
Eichenbaum, H., Mathews, P., & Cohen, N. J. (1989) · Behavioral Neuroscience · doi:10.1037/0735-7044.103.6.1207 · Cited by 183 · see citing works
Effects of intrauterine inflammation on developing rat brain
Bell, M. J., & Hallenbeck, J. M. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10423 · Cited by 182 · see citing works
Inflammatory Mediators and Neonatal Brain Damage
Saliba, É., & Henrot, A. (2001) · Neonatology · doi:10.1159/000047096 · Cited by 156 · see citing works
Giese, K.-P., Friedman, E. L., Telliez, J., Fedorov, N. B., Wines, M., Feig, L. A., & Silva, A. J. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00096-x · Cited by 138 · see citing works
Prior treatment effects on open field behaviour of mice — A genetic analysis
Henderson, N. D. (1967) · Animal Behaviour · doi:10.1016/0003-3472(67)90023-1 · Cited by 122 · see citing works
Zhou, L., & Shine, H. D. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10718 · Cited by 121 · see citing works
TNFα contributes to the death of NGF-dependent neurons during development
Barker, V., Middleton, G., Davey, F. D., & Davies, A. M. (2001) · Nature Neuroscience · doi:10.1038/nn755 · Cited by 108 · see citing works
Recognition memory in rats—II. Neuroanatomical substrates
Steckler, T., Drinkenburg, W. H. I. M., Sahgal, A., & Aggleton, J. P. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00061-0 · Cited by 108 · see citing works
Aloe, L., Properzi, G., Probert, L., Akassoglou, K., Kassiotis, G., Micera, A., & Fiore, M. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01748-5 · Cited by 102 · see citing works
Role of nerve growth factor and other trophic factors in brain inflammation
Villoslada, P., & Genain, C. P. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)46025-1 · Cited by 96 · see citing works
Interactions of Ro 15-4513 with diazepam, sodium pentobarbital and ethanol in a holeboard test
Lister, R. G. (1987) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(87)90015-3 · Cited by 64 · see citing works
Potential role of synaptopodin in spine motility by coupling actin to the spine apparatus
Deller, T., Mundel, P. H., & Frotscher, M. (2000) · Hippocampus · doi:10.1002/1098-1063(2000)10:5 · Cited by 61 · see citing works
Jurič, D. M., & Čarman‐Kržan, M. (2001) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(01)00044-2 · Cited by 46 · see citing works
Expression of regeneration-related molecules in injured and regenerating striatal and nigral neurons
Chaisuksunt, V., Campbell, G., Zhang, Y., et al. (2003) · Journal of Neurocytology · doi:10.1023/b:neur.0000005601.59097.24 · Cited by 22 · see citing works
Rondi‐Reig, L., Lemaigre‐Dubreuil, Y., Montécot, C., et al. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00050-1 · Cited by 22 · see citing works
Levav, T., Saar, T., Berkovich, L., et al. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.03.004 · Cited by 19 · see citing works
van Eden, C. G., & Rinkens, A. (1994) · Developmental Brain Research · doi:10.1016/0165-3806(94)90159-7 · Cited by 12 · see citing works
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Mor, G., & Cardenas, I. (2010) · American Journal of Reproductive Immunology · doi:10.1111/j.1600-0897.2010.00836.x · Cited by 1,431 · see citing works
Immune involvement in schizophrenia and autism: Etiology, pathology and animal models
Patterson, P. H. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.12.016 · Cited by 766 · see citing works
Early-life programming of later-life brain and behavior: a critical role for the immune system
Bilbo, S. D. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.014.2009 · Cited by 652 · see citing works
Boksa, P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.03.005 · Cited by 603 · see citing works
Goines, P. E., Croen, L. A., Braunschweig, D., Yoshida, C. K., Grether, J., Hansen, R., Kharrazi, M., Ashwood, P., & Van de Water, J. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-13 · Cited by 351 · see citing works
Beumer, W., Gibney, S. M., Drexhage, R. C., Pont-Lezica, L., Doorduin, J., Klein, H. C., Steiner, J., Connor, T. J., Harkin, A., Versnel, M. A., et al. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0212100 · Cited by 347 · see citing works
Meyer, U., Yee, B. K., & Feldon, J. (2007) · The Neuroscientist · doi:10.1177/1073858406296401 · Cited by 303 · see citing works
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
Oskvig, D. B., Elkahloun, A. G., Johnson, K. R., Phillips, T. M., & Herkenham, M. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.015 · Cited by 248 · see citing works
Bilbo, S. D., Biedenkapp, J. C., Der-Avakian, A., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1748-05.2005 · Cited by 251 · see citing works
“For example, perinatal endotoxin administration induces cytokine expression, apoptosis, and glial activation in the immature rat brain, factors that have been linked to white matter injury (Cai et al., 2003; Golan et al., 2005).”
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Arrode-Brusés, G., & Brusés, J. L. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-83 · Cited by 146 · see citing works
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Roumier, A., Pascual, O., Béchade, C., Wakselman, S., Poncer, J.-C., Réal, E., Triller, A., & Bessis, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002595 · Cited by 146 · see citing works
Madore, C., Leyrolle, Q., Lacabanne, C., Benmamar-Badel, A., Joffre, C., Nadjar, A., & Layé, S. (2016) · Neural Plasticity · doi:10.1155/2016/3597209 · Cited by 141 · see citing works
Neurodevelopmental damage after prenatal infection: role of oxidative stress in the fetal brain
Lanté, F., Meunier, J., Guiramand, J., Maurice, T., Cavalier, M., de Jesus Ferreira, M.-C., Aimar, R., Cohen-Solal, C., Vignes, M., & Barbanel, G. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.027 · Cited by 140 · see citing works
Early prenatal exposure to LPS results in anxiety- and depression-related behaviors in adulthood
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Lanté, F., Meunier, J., Guiramand, J., De Jesus Ferreira, M., Cambonie, G., Aimar, R., Cohen‐Solal, C., Maurice, T., Vignes, M., & Barbanel, G. (2008) · Hippocampus · doi:10.1002/hipo.20421 · Cited by 124 · see citing works
Arsenault, D., St-Amour, I., Cisbani, G., Rousseau, L.-S., & Cicchetti, F. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.12.016 · Cited by 118 · see citing works
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Piontkewitz, Y., Arad, M., & Weiner, I. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.04.019 · Cited by 108 · see citing works
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Michel, M., Schmidt, M. J., & Mirnics, K. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22044 · Cited by 107 · see citing works
Murphy, T. K., Storch, E. A., Turner, A., Reid, J. M., Tan, J., & Lewin, A. B. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.017 · Cited by 87 · see citing works
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Hodyl, N. A., Aboustate, N., Bianco-Miotto, T., Roberts, C. T., Clifton, V. L., & Stark, M. J. (2017) · Placenta · doi:10.1016/j.placenta.2017.06.009 · Cited by 76 · see citing works
Kirsten, T. B., Chaves-Kirsten, G. P., Bernardes, S., Scavone, C., Sarkis, J. E., Bernardi, M. M., & Felicio, L. F. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134565 · Cited by 65 · see citing works
Breen, M. S., Wingo, A. P., Koen, N., Donald, K. A., Nicol, M., Zar, H. J., Ressler, K. J., Buxbaum, J. D., & Stein, D. J. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.05.016 · Cited by 35 · see citing works
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. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.05.058 · Cited by 33 · see citing works
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Golan, H., Stilman, M., Lev, V., & Huleihel, M. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.05.045 · Cited by 32 · see citing works
Patil, J., Matte, A., Mallard, C., & Sandberg, M. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2016.1221496 · Cited by 22 · see citing works
- Authors
- Golan, H. M., Lev, V., Hallak, M., Sorokin, Y., & Huleihel, M.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Hutzel Women's Hospital (US)
- Corresponding author
- Golan, H.M.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 48
- Issue
- 6
- Pages
- 903-917
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2041442674
- Cited by
- 253
- References
- 50
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 17 · 2019: 11 · 2018: 14 · 2017: 8 · 2016: 11 · 2015: 19 · 2014: 15 · 2013: 15 · 2012: 19
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ben-Gurion University of the Negev
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- maternal inflammation, intrauterine inflammation, brain development, hippocampus, pyramidal neurons, granular cells, lipopolysaccharide, inflammatory cytokines, learning and memory impairment, fetal brain development, cerebral cortex, cerebellum, neuroinflammation
- MeSH terms
- Age Factors, Animals, Behavior, Animal, Body Weight, Brain, Brain Chemistry, Cell Count, Exploratory Behavior, Female, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Neurons, Organ Size, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Psychomotor Performance, Reaction Time, Reflex, Spleen, Time Factors, Gene Expression Regulation, Developmental, Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Embryonic Development, Mice
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