Normal aging of offspring mice of mothers with induced 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. In the present study we tested the possibility that prenatal exposure to a high level of inflammatory factors may increase the risk for neurodegeneration in aging. The effect of systemic maternal inflammation (MI), induced by lipopolysaccharide (LPS) on offspring brain aging, was examined in 8 month old (adult) and 20 month old (aged) offspring mice. A significant effect of age was found in the distance and velocity of exploration in the open field in both groups. In addition, MI aged offspring covered longer distances and enter frequently to the center of the field compared with the aged control group. Although only little difference was found in the aged MI offspring compared with the control offspring, the overall profile of behavior of these mice differs from that of the control group, as detected by clustering analysis. The expression of the death-associated protein FAS-ligand and the amount of apoptotic cell death were examined in the brains of aged offspring. Similar levels of FAS-ligand expression and parallel density of apoptotic cells were detected in the brains of aged mice of control and MI groups. Altogether, moderate systemic MI was not found to increase the risk for cell death in the aged offspring; limited effect was found in mice profile of behavior.
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Prenatal LPS exposure increased open field activity at 20 months of age.
“Offspring exposed to LPS during prenatal development were more active in the open field test at 20 months of age (Golan et al., 2006).”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Golan et al., 2006
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
The use of a plus-maze to measure anxiety in the mouse
Lister, R. G. (1987) · Psychopharmacology · doi:10.1007/bf00177912 · Cited by 2,617 · see citing works
Dinarello, C. A. (2000) · CHEST Journal · doi:10.1378/chest.118.2.503 · Cited by 2,047 · 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
(2000) · Cited by 919 · see citing works
Interleukin-6 and risk of cognitive decline: MacArthur Studies of Successful Aging
Weaver, J. D., Huang, M.-H., Albert, M., Harris, T., Rowe, J. W., & Seeman, T. E. (2002) · Neurology · doi:10.1212/wnl.59.3.371 · Cited by 536 · see citing works
Age-related changes in speed of walking
Himann, J. E., Cunningham, D. A., Rechnitzer, P. A., & Paterson, D. H. (1988) · Medicine & Science in Sports & Exercise · doi:10.1249/00005768-198820020-00010 · Cited by 518 · 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
Ader, R., Weijnen, J. A. W. M., & Moleman, P. (1972) · Psychonomic Science · doi:10.3758/bf03335453 · Cited by 432 · see citing works
Monocyte Cytokine Production in an Elderly Population: Effect of Age and Inflammation
Roubenoff, R., Harris, T. B., Abad, L. W., Wilson, P. W. F., Dallal, G. E., & Dinarello, C. A. (1998) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/53a.1.m20 · Cited by 418 · see citing works
Blasko, I., Stampfer‐Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P., & Grubeck‐Loebenstein, B. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00101.x · Cited by 374 · 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
Rogers, D. C., Jones, D. N. C., Nelson, P. R., Jones, C. M., Quilter, C. A., Robinson, T. L., & Hagan, J. J. (1999) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00072-8 · Cited by 294 · 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
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
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
Plasma cytokine profiles in elderly humans
Forsey, R. J., Thompson, J. M., Ernerudh, J., HURST, T. L., Strindhall, J., Johansson, B. E. A., Nilsson, B.-O., & Wikby, A. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00025-3 · Cited by 249 · 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
Lukiw, W. J. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000023615.89699.63 · Cited by 172 · 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
Martin, D. S. D., Lonergan, P. E., Boland, B., Fogarty, M. P., Brady, M., Horrobin, D. F., Campbell, V. A., & Lynch, M. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205289200 · Cited by 151 · see citing works
Alterations in behavior in adult offspring mice following maternal inflammation during pregnancy
Hava, G., Lev, V., Yael, M., Hallak, M., & Mahoud, H. (2006) · Developmental Psychobiology · doi:10.1002/dev.20116 · Cited by 146 · see citing works
Shetty, A. K., & Turner, D. A. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980504)394:2 · Cited by 129 · 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
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
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
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
Su, J. H., Anderson, A. J., Cribbs, D. H., Tu, C. H., Tong, L., Kesslak, P. J., & Cotman, C. W. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(02)00019-0 · Cited by 91 · see citing works
Increased cerebrospinal fluid Fas (Apo-1) levels in Alzheimer’s disease
Martı́nez, M., Fernández-Vivancos, E., Frank, A., la Fuente, M. D., & Hernánz, Á. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02363-5 · Cited by 80 · see citing works
Ferguson, S. A., & Gray, E. P. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.06.009 · Cited by 73 · see citing works
Could a deficiency in growth hormone signaling be beneficial to the aging brain?
Kinney-Forshee, B. A., Kinney, N. E., Steger, R. W., & Bartke, A. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2003.10.018 · Cited by 71 · see citing works
Age-related loss of calcium binding proteins in rabbit hippocampus
de Jong, G. I., Naber, P. A., van der Zee, E. A., Thompson, L. T., Disterhoft, J. F., & Luiten, P. G. M. (1996) · Neurobiology of Aging · doi:10.1016/0197-4580(96)00030-9 · Cited by 66 · 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
Impact of perinatal asphyxia on the GABAergic and locomotor system
van de Berg, W. D. J., Kwaijtaal, M., de Louw, A. J. A., Lissone, N. P. A., Schmitz, C., Faull, R. L. M., Blokland, A., Blanco, C. E., & Steinbusch, H. W. M. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00787-x · Cited by 62 · see citing works
Shi, L., Argenta, A. E., Winseck, A. K., & Brunso‐Bechtold, J. K. (2004) · The Journal of Comparative Neurology · doi:10.1002/cne.20303 · Cited by 61 · see citing works
Teunis, M., Heijnen, C. J., Sluyter, F., Bakker, J. M., van Dam, A., Hof, M., Cools, A. R., & Kavelaars, A. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00351-x · Cited by 47 · see citing works
Decreased anxiety levels related to aging
Torras-García, M., Costa‐Miserachs, D., Coll-Andreu, M., & Portell-Cortés, I. (2005) · Experimental Brain Research · doi:10.1007/s00221-005-2240-y · Cited by 44 · see citing works
Dell’Anna, E., Geloso, M. C., Magarelli, M., & Molinari, M. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12733-6 · Cited by 38 · see citing works
GERSTEIN, M., Huleihel, M., Mane, R., Stilman, M., Kashtuzki, I., Hallak, M., & Golan, H. M. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.06.019 · Cited by 30 · see citing works
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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
Boksa, P. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.03.005 · Cited by 603 · see citing works
Hagberg, H., Gressèns, P., & Mallard, C. E. (2011) · Annals of Neurology · doi:10.1002/ana.22620 · Cited by 519 · see citing works
Bronson, S. L., & Bale, T. L. (2014) · Endocrinology · doi:10.1210/en.2014-1040 · Cited by 299 · 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
Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring
de Cossío, L. F., Guzman, A. S., van der Veldt, S., & Luheshi, G. N. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.09.028 · Cited by 214 · see citing works
Wischhof, L., Irrsack, E., Osorio, C., & Koch, M. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.10.004 · Cited by 158 · see citing works
Giovanoli, S., Notter, T., Richetto, J., Labouesse, M. A., Vuillermot, S., Riva, M. A., & Meyer, U. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0437-y · 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
Hao, L.-Y., Hao, X. Q., Li, S. H., & Li, X. H. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.006 · Cited by 93 · see citing works
Aguilar-Valles, A., Rodrigue, B., & Matta-Camacho, E. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00852 · Cited by 62 · see citing works
Wang, H., Meng, X., Ning, H., Zhao, X., Wang, Q., Liu, P., Zhang, H., Zhang, C., Chen, G.-H., & Xu, D. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.10.030 · Cited by 58 · see citing works
Rana, S. A., Aavani, T., & Pittman, Q. J. (2012) · Hormones and Behavior · doi:10.1016/j.yhbeh.2012.03.015 · Cited by 54 · see citing works
Chen, G.-H., Wang, H., Yang, Q., Tao, F., Wang, C., & Xu, D. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.001 · Cited by 53 · see citing works
Zager, A., Peron, J. P. S., Mennecier, G., Rodrigues, S. C., Aloia, T. P. A., & Palermo‐Neto, J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.07.021 · Cited by 45 · see citing works
Lipopolysaccharide injected to pregnant mice affects behavior of their offspring in adulthood
Natalia, C., Gajerska, M., Bartkowska, K., Turlejski, K., & Djavadian, R. L. (2011) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2011-1868 · Cited by 37 · see citing works
Leyrolle, Q., Decoeur, F., Brière, G., Amadieu, C., Quadros, A. R. A. D. A., Voytyuk, I., Lacabanne, C., Benmamar‐Badel, A., Bourel, J., Aubert, A., et al. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00793-7 · Cited by 33 · see citing works
Zaman, V., Boger, H. A., Granholm, A., Rohrer, B., Moore, A., Buhusi, M. C., Gerhardt, G. A., Hoffer, B. J., & Middaugh, L. D. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06456.x · Cited by 33 · see citing works
Zager, A., Mennecier, G., & Palermo‐Neto, J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.03.036 · Cited by 27 · see citing works
Konefal, S., & Stellwagen, D. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0160 · Cited by 25 · see citing works
Prieto‐Villalobos, J., Alvear, T. F., Liberona, A., Lucero, C. M. J., Martínez-Araya, C. J., Balmazabal, J., Inostroza, C. A., Ramírez, G., Gómez, G. I., & Orellana, J. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179503 · Cited by 21 · see citing works
Wang, F., Zhang, Z., Cao, L., Yang, Q., Lu, Q., & Chen, G. (2020) · Brain and Behavior · doi:10.1002/brb3.1546 · Cited by 17 · see citing works
Spulber, S. D., Bartfai, T., Winblad, B. G., & Schultzberg, M. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22534 · Cited by 14 · see citing works
Zager, A., Andersen, M. L., Tufik, S., & Palermo‐Neto, J. (2013) · NeuroImmunoModulation · doi:10.1159/000355466 · Cited by 14 · see citing works
Zager, A., Pinheiro, M. L., Ferraz-de-Paula, V., Ribeiro, A., & Palermo‐Neto, J. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.08.007 · Cited by 14 · see citing works
Kumar, U., & Mohanty, B. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.09.011 · Cited by 13 · see citing works
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Smith, S. E. P., Hsiao, E. Y., & Patterson, P. H. (2010) · Springer eBooks · doi:10.1007/978-1-60327-921-5_7 · Cited by 11 · see citing works
Arsenault, D., Coulombe, K., Zhu, A., Gong, C., Kil, K.-E., Choi, J., Poutiainen, P., & Brownell, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142093 · Cited by 7 · see citing works
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Smith, S. E. P., & Patterson, P. H. (2008) · Springer eBooks · doi:10.1007/978-0-387-84851-8_7 · Cited by 7 · see citing works
Zou, P., Huang, Z., Zong, X., & Zhang, Q. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106436 · Cited by 5 · see citing works
Zager, A. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2013.tde-21112013-113642
- Authors
- Golan, H., Stilman, M., Lev, V., & Huleihel, M.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Golan, H.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2006
- Volume
- 141
- Issue
- 4
- Pages
- 1909-1918
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2074075153
- Cited by
- 32
- References
- 39
- Citations by year
- 2025: 1 · 2021: 1 · 2020: 3 · 2019: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 2
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- prenatal inflammation, brain aging, neurodegeneration, offspring behavior, open field exploration, Fas ligand, apoptosis, cognitive aging
- MeSH terms
- Age Factors, Aging, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Brain, Exploratory Behavior, Female, Gestational Age, Immunohistochemistry, Inflammation, Learning, Lipopolysaccharides, Motor Activity, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Cytokines, Cell Death, Mice, Fas Ligand Protein
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