Maternal separation with early weaning: A novel mouse model of early life neglect
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BACKGROUND: Childhood adversity is associated with increased risk for mood, anxiety, impulse control, and substance disorders. Although genetic and environmental factors contribute to the development of such disorders, the neurobiological mechanisms involved are poorly understood. A reliable mouse model of early life adversity leading to lasting behavioral changes would facilitate progress in elucidating the molecular mechanisms underlying these adverse effects. Maternal separation is a commonly used model of early life neglect, but has led to inconsistent results in the mouse. RESULTS: In an effort to develop a mouse model of early life neglect with long-lasting behavioral effects in C57BL/6 mice, we designed a new maternal separation paradigm that we call Maternal Separation with Early Weaning (MSEW). We tested the effects of MSEW on C57BL/6 mice as well as the genetically distinct DBA/2 strain and found significant MSEW effects on several behavioral tasks (i.e., the open field, elevated plus maze, and forced swim test) when assessed more than two months following the MSEW procedure. Our findings are consistent with MSEW causing effects within multiple behavioral domains in both strains, and suggest increased anxiety, hyperactivity, and behavioral despair in the MSEW offspring. Analysis of pup weights and metabolic parameters showed no evidence for malnutrition in the MSEW pups. Additionally, strain differences in many of the behavioral tests suggest a role for genetic factors in the response to early life neglect. CONCLUSIONS: These results suggest that MSEW may serve as a useful model to examine the complex behavioral abnormalities often apparent in individuals with histories of early life neglect, and may lead to greater understanding of these later life outcomes and offer insight into novel therapeutic strategies.
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Neglected rodents exhibited significantly elevated corticosterone levels, indicating a dysregulated HPA axis response and heightened sensitivity to stress.
“The same rodents also exhibited significantly elevated corticosterone levels, indicating a dysregulated HPA axis response and, thus, heightened sensitivity to stress.”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [145]
The Results (Effects of MSEW; page not provided) report no significant effect of maternal separation with early weaning on serum corticosterone at either measured age. The Discussion likewise says there was no MSEW-induced increase in corticosterone, contrary to the claimed significant elevation and its proposed HPA-axis interpretation. (LLM, conf=0.93)
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Experimental — accuracy not yet measuredNeglected rodent offspring have shown increased susceptibility to anxiety and depressive-like behaviors when exposed to stress in both adolescence and adulthood.
“Neglected rodent offspring have shown increased susceptibility to anxiety and depressive-like behaviors when exposed to stress in both adolescence and adulthood (145, 146).”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [145]
The Discussion reports increased anxiety-like behavior after maternal separation with early weaning and increased depressive-like behavior in D2 mice on the forced swim test; B6 mice were relatively unaffected on that test. The Results (Behavioral Testing; page unavailable) state that mice were tested at 65–80 days of age, not during adolescence. The Discussion also describes enhanced vulnerability under higher stress as a possibility requiring further research, rather than an established result. (LLM, conf=0.90)
Experimental — accuracy not yet measuredMSEW increases both anxiety levels and hyperactivity in adulthood.
“This developmental manipulation has been shown to increase both anxiety levels and hyperactivity in adulthood (11), suggesting it has strong translational validity”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [11]
The combination of early weaning with maternal separation results in increased hyperactivity in mice.
“The combination of early weaning with maternal separation also results in increased hyperactivity in mice (11).”
From Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity (2019) · cites this paper as [11]
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Cites
Mixed-Effects Models in Sand S-PLUS
Pinheiro, J. C., & Bates, D. M. (2000) · Statistics and Computing · doi:10.1007/978-1-4419-0318-1 · Cited by 11,187 · see citing works
Mixed-Effects Models in S and S-PLUS
(2001) · Technometrics · doi:10.1198/tech.2001.s574 · Cited by 9,278 · see citing works
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531 · see citing works
Behavioral despair in mice: a primary screening test for antidepressants.
Porsolt, R. D., Bertin, A., & Jalfre, M. (1977) · PubMed · Cited by 3,275 · see citing works
Behavioural despair in rats: A new model sensitive to antidepressant treatments
Porsolt, R. D., Anton, G., Blavet, N., & Jalfre, M. (1978) · European Journal of Pharmacology · doi:10.1016/0014-2999(78)90118-8 · Cited by 3,138 · 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
The open-field test: A critical review.
WALSH, R. N., & Cummins, R. A. (1976) · Psychological Bulletin · doi:10.1037/0033-2909.83.3.482 · Cited by 2,389 · see citing works
Widom, C. S. (1989) · Science · doi:10.1126/science.2704995 · Cited by 1,976 · see citing works
Applied Mixed Models in Medicine
Brown, H., & Presco, R. (2000) · Technometrics · doi:10.1080/00401706.2000.10485742 · Cited by 1,699 · see citing works
Genetics of Mouse Behavior: Interactions with Laboratory Environment
Crabbe, J. C., Wahlsten, D., & Dudek, B. C. (1999) · Science · doi:10.1126/science.284.5420.1670 · Cited by 1,666 · see citing works
Caldji, C., Tannenbaum, B., Sharma, S., Francis, D., Plotsky, P. M., & Meaney, M. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5335 · Cited by 1,437 · see citing works
Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey
Molnar, B. E., Buka, S. L., & Kessler, R. C. (2001) · American Journal of Public Health · doi:10.2105/ajph.91.5.753 · Cited by 1,193 · see citing works
Design and Analysis of Group-Randomized Trials
Sonnad, S. S. (1999) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199902000-00025 · Cited by 1,130 · see citing works
Design and Analysis of Group-Randomized Trials
Murray, D. M. (2007) · doi:10.1093/oso/9780195120363.001.0001 · Cited by 1,114 · see citing works
Spatz Widom, C., DuMont, K., & Czaja, S. J. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.1.49 · Cited by 1,059 · see citing works
Child neglect: developmental issues and outcomes☆
Hildyard, K. L., & Wolfe, D. A. (2002) · Child Abuse & Neglect · doi:10.1016/s0145-2134(02)00341-1 · Cited by 994 · see citing works
Sapolsky, R. M., & Meaney, M. J. (1986) · Brain Research Reviews · doi:10.1016/0165-0173(86)90010-x · Cited by 991 · see citing works
The relation between fear induced by novel stimulation and exploratory drive.
Montgomery, K. C. (1955) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0043788 · Cited by 916 · see citing works
Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J. R., & Plotsky, P. M. (2010) · Developmental Neuroscience · doi:10.1159/000111395 · Cited by 878 · see citing works
Social supports and serotonin transporter gene moderate depression in maltreated children
Kaufman, J., Yang, B., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D. S., Krystal, J. H., & Gelernter, J. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404376101 · Cited by 801 · see citing works
Choleris, E. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00011-2 · Cited by 761 · see citing works
Kaufman, J., Yang, B.-Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., Krystal, J. H., & Gelernter, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.026 · Cited by 692 · see citing works
Do early‐life events permanently alter behavioral and hormonal responses to stressors?
Anisman, H., Zaharia, M. D., Meaney, M. J., & Merali, Z. (1998) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(98)00025-2 · Cited by 654 · see citing works
Developmental determinants of sensitivity and resistance to stress
Levine, S. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.03.013 · Cited by 574 · see citing works
Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats
Aisa, B., Tordera, R. M., Lasheras, B., Rı́o, J. D., & Ramírez, M. J. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.12.013 · Cited by 534 · see citing works
Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research
National Research Council (2003) · National Academies Press eBooks · doi:10.17226/10732 · Cited by 530 · see citing works
Lucki, I., Dalvi, A., & Mayorga, A. J. (2001) · Psychopharmacology · doi:10.1007/s002130100694 · Cited by 506 · see citing works
Maxfield, M. G. (1996) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1996.02170290056009 · Cited by 504 · see citing works
Kalinichev, M., Easterling, K. W., Plotsky, P. M., & Holtzman, S. G. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00781-5 · Cited by 484 · see citing works
Champagne, F., & Meaney, M. J. (2001) · Progress in Brain Research · doi:10.1016/s0079-6123(01)33022-4 · Cited by 455 · see citing works
Differences in fear motivated behaviors among inbred mouse strains
Trullás, R., & Skolnick, P. (1993) · Psychopharmacology · doi:10.1007/bf02244948 · Cited by 451 · see citing works
Applied Mixed Models in Medicine
Ziegel, E. R., Brown, H. K., & Prescott, R. J. (2000) · Technometrics · doi:10.2307/1270978 · Cited by 451 · see citing works
Long-term Biobehavioral Effects of Maternal Separation in the Rat: Consistent or Confusing?
Lehmann, J., & Feldon, J. (2000) · Reviews in the Neurosciences · doi:10.1515/revneuro.2000.11.4.383 · Cited by 447 · see citing works
Childhood and Adolescent Depression
Bhatia, S. K., & Bhatia, S. C. (2011) · PsycEXTRA Dataset · doi:10.1037/e552642011-001 · Cited by 447 · see citing works
Wigger, A., & Neumann, I. D. (1999) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00300-x · Cited by 443 · see citing works
Griebel, G., Belzung, C., Perrault, G., & Sanger, D. J. (2000) · Psychopharmacology · doi:10.1007/s002130050038 · Cited by 420 · see citing works
Millstein, R. A., & Holmes, A. (2007) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.05.003 · Cited by 407 · see citing works
Long‐term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences
Võikar, V., Polus, A., Vasar, E., & Rauvala, H. (2004) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2004.00106.x · Cited by 359 · see citing works
Ethology and psychopharmacology
(1995) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(95)90084-5 · Cited by 317 · see citing works
Early life genetic, epigenetic and environmental factors shaping emotionality in rodents
Holmes, A., Guisquet, A. M. L., Vogel, E., Millstein, R. A., Leman, S., & Belzung, C. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.012 · Cited by 296 · see citing works
Suchecki, D., Rosenfeld, P., & Levine, S. (1993) · Developmental Brain Research · doi:10.1016/0165-3806(93)90022-3 · Cited by 276 · see citing works
Holmes, A., Wrenn, C. C., Harris, A. P., Thayer, K. E., & Crawley, J. N. (2002) · Genes Brain & Behavior · doi:10.1046/j.1601-1848.2001.00005.x · Cited by 275 · see citing works
Parental Depression: Animal Models of an Adverse Life Event
Newport, D. J., Stowe, Z. N., & Nemeroff, C. B. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.8.1265 · Cited by 265 · see citing works
McIntosh, J. F., Anisman, H., & Merali, Z. (1999) · Developmental Brain Research · doi:10.1016/s0165-3806(99)00005-x · Cited by 255 · see citing works
TNFα Signaling in Depression and Anxiety: Behavioral Consequences of Individual Receptor Targeting
Simen, B. B., Duman, C. H., Simen, A. A., & Duman, R. S. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.013 · Cited by 249 · see citing works
Self-citationEndocrine responses to mother‐infant separation in developing rats
Kuhn, C. M., Pauk, J. S., & Schanberg, S. M. (1990) · Developmental Psychobiology · doi:10.1002/dev.420230503 · Cited by 242 · see citing works
Macrı̀, S., Mason, G. J., & Würbel, H. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03541.x · Cited by 240 · see citing works
Widom, C. S., WHITE, H. R., Czaja, S. J., & Marmorstein, N. R. (2007) · Journal of Studies on Alcohol and Drugs · doi:10.15288/jsad.2007.68.317 · Cited by 224 · see citing works
Attention-deficit/hyperactivity disorder symptoms and child maltreatment: a population-based study
Ouyang, L., Fang, X., Mercy, J., Perou, R., & Grosse, S. D. (2008) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2008.06.002 · Cited by 221 · see citing works
Genetic and Environmental Predictors of Early Alcohol Use
Kaufman, J., Yang, B.-Z., Douglas-Palumberi, H., Crouse-Artus, M., Lipschitz, D., Krystal, J. H., & Gelernter, J. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.039 · Cited by 216 · see citing works
Postweaning Development of Negative Feedback in the Pituitary-Adrenal System of the Rat
Goldman, L., Winget, C., Hollingshead, G. W., & Levine, S. D. (2008) · Neuroendocrinology · doi:10.1159/000122169 · Cited by 202 · see citing works
Antidepressant-like effects in various mice strains in the forced swimming test
David, D. J. P., Renard, C. E., Jolliet, P., Hascoët, M., & Bourin, M. (2003) · Psychopharmacology · doi:10.1007/s00213-002-1335-4 · Cited by 183 · see citing works
Bouwknecht, J. A., Spiga, F., Staub, D. R., Hale, M. W., Shekhar, A., & Lowry, C. A. (2007) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2006.12.009 · Cited by 183 · see citing works
Importance of Early Neglect for Childhood Aggression
Kotch, J. B., Lewis, T., Hussey, J. M., English, D., Thompson, R., Litrownik, A. J., Runyan, D. K., Bangdiwala, S. I., Margolis, B., & Dubowitz, H. (2008) · Pediatrics · doi:10.1542/peds.2006-3622 · Cited by 183 · see citing works
van Oers, H. J. J., de Kloet, E. R., & Levine, S. D. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00143-6 · Cited by 177 · see citing works
Childhood trauma and obsessive-compulsive symptoms
Mathews, C. A., Kaur, N., & Stein, M. B. (2007) · Depression and Anxiety · doi:10.1002/da.20316 · Cited by 161 · see citing works
New replicable anxiety-related measures of wall vs. center behavior of mice in the open field
Lipkind, D., Sakov, A., Kafkafi, N., Elmer, G. I., Benjamini, Y., & Golani, I. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00148.2004 · Cited by 143 · see citing works
Ducottet, C., & Belzung, C. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.05.018 · Cited by 143 · see citing works
Effects of Maternal Deprivation on the ACTH Stress Response in the Infant Rat
Suchecki, D., Mozaffarian, D., Gross, G., Rosenfeld, P., & Levine, S. D. (2008) · Neuroendocrinology · doi:10.1159/000126361 · Cited by 141 · see citing works
Neurobiology of early life stress: Rodent studies
Gutman, D. A., & Nemeroff, C. B. (2002) · Seminars in Clinical Neuropsychiatry · doi:10.1053/scnp.2002.31781 · Cited by 137 · see citing works
Podhorná, J., & Brown, R. E. (2002) · Genes Brain & Behavior · doi:10.1034/j.1601-183x.2002.10205.x · Cited by 134 · see citing works
Repeated maternal separation does not alter sucrose-reinforced and open-field behaviors
Shalev, U., & Kafkafi, N. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00756-6 · Cited by 126 · see citing works
Rosenfeld, P., Wetmore, J. B., & Levine, S. D. (1992) · Physiology & Behavior · doi:10.1016/0031-9384(92)90415-x · Cited by 122 · see citing works
Weaver, I. C. G., Szyf, M., & Meaney, M. J. (2002) · Endocrine Research · doi:10.1081/erc-120016989 · Cited by 121 · see citing works
Ohl, F., Roedel, A., Binder, E., & Holsboer, F. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02436.x · Cited by 110 · see citing works
Macrı̀, S., Chiarotti, F., & Würbel, H. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.031 · Cited by 109 · see citing works
Colorado, R. A., Shumake, J., Conejo, N. M., González‐Pardo, H., & Gonzalez-Lima, F. (2005) · Behavioural Processes · doi:10.1016/j.beproc.2005.09.007 · Cited by 106 · see citing works
Maternal regulation of the adrenocortical response in preweanling rats
Rosenfeld, P., Gutierrez, Y. A., Martin, A. M., Mallett, H. A., Alleva, E., & Levine, S. D. (1991) · Physiology & Behavior · doi:10.1016/0031-9384(91)90001-5 · Cited by 105 · see citing works
Early weaning induces anxiety and aggression in adult mice
Kikusui, T., Takeuchi, Y., & Mori, Y. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2003.12.016 · Cited by 103 · see citing works
Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans
Mahoney, L. B., Denny, C. A., & Seyfried, T. N. (2006) · Lipids in Health and Disease · doi:10.1186/1476-511x-5-13 · Cited by 98 · see citing works
Cook, M. N., Williams, R. W., & Flaherty, L. A. (2001) · Behavioral Neuroscience · doi:10.1037/0735-7044.115.2.468 · Cited by 91 · see citing works
Cirulli, F., Santucci, D., Giovanni Laviola, A., Alleva, E., & Levine, S. D. (1994) · Developmental Psychobiology · doi:10.1002/dev.420270505 · Cited by 90 · see citing works
Cannizzaro, C., Plescia, F., Martire, M., Gagliano, M., Cannizzaro, G., Mantia, G., & Cannizzaro, E. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.12.010 · Cited by 85 · see citing works
Early weaning augments neuroendocrine stress responses in mice
Kikusui, T., Nakamura, K., Kakuma, Y., & Mori, Y. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.08.007 · Cited by 82 · see citing works
Millstein, R. A., Ralph, R. J., Yang, R. J., & Holmes, A. (2006) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00172.x · Cited by 82 · see citing works
Schmidt, M. V., Levine, S., Oitzl, M., van der Mark, M. H., Müller, M., Holsboer, F., & de Kloet, E. D. (2005) · Endocrinology · doi:10.1210/en.2004-1042 · Cited by 80 · see citing works
Rodgers, R. J., & Cole, J. C. (1994) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)90124-4 · Cited by 77 · see citing works
Caldarone, B. J., Karthigeyan, K., Harrist, A. V., Hunsberger, J. G., Wittmack, E. K., King, S. L., Jatlow, P. I., & Picciotto, M. R. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1518-7 · Cited by 76 · see citing works
Pascual, R., & Zamora-León, S. (2007) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2007-1663 · Cited by 74 · see citing works
van Oers, H. V., de Kloet, E. D., & Levine, S. (1997) · Stress · doi:10.3109/10253899709013745 · Cited by 73 · see citing works
Alcaro, A., Cabib, S., Ventura, R., et al. (2002) · Psychopharmacology · doi:10.1007/s00213-002-1161-8 · Cited by 72 · see citing works
The Ontogeny of Glucocorticoid Negative Feedback: Influence of Maternal Deprivation1
van Oers, H. J. J., de Kloet, E. R., Li, C., & Levine, S. D. (1998) · Endocrinology · doi:10.1210/endo.139.6.6037 · Cited by 70 · see citing works
Early life programming of fear conditioning and extinction in adult male rats
Stevenson, C. W., Spicer, C. H., Mason, R., & Marsden, C. A. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.08.005 · Cited by 62 · see citing works
Enthoven, L., Oitzl, M. S., Koning, N. R., van der Mark, M. H., & de Kloet, E. R. (2008) · Endocrinology · doi:10.1210/en.2008-0238 · Cited by 60 · see citing works
Sugimoto, Y., Kajiwara, Y., Hirano, K., Yamada, S., Tagawa, N., Kobayashi, Y., Hotta, Y., & Yamada, J. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.07.005 · Cited by 55 · see citing works
Impact of intra‐ and interstrain cross‐fostering on mouse maternal care
Van Der Veen, R., Abrous, D. N., Ronald de Kloet, E., Piazza, P. V., & Koehl, M. (2008) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2007.00337.x · Cited by 54 · see citing works
Parfitt, D. B., WALTON, J., Corriveau, E. A., & Helmreich, D. L. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.06.002 · Cited by 51 · see citing works
Troakes, C., & Ingram, C. D. (2008) · Stress · doi:10.1080/10253890802506391 · Cited by 47 · see citing works
Anxiety in the Elevated Zero-Maze Is Augmented in Mice After Repeated Daily Exposure
Cook, M. N., Crounse, M., & Flaherty, L. A. (2002) · Behavior Genetics · doi:10.1023/a:1015249706579 · Cited by 43 · see citing works
Enthoven, L., de Kloet, E. R., & Oitzl, M. S. (2008) · Brain Research · doi:10.1016/j.brainres.2008.04.009 · Cited by 37 · see citing works
Alcohol abuse among U.S. Navy recruits who were maltreated in childhood
Trent, L., Stander, V. A., Thomsen, C. J., & Merrill, L. (2007) · Alcohol and Alcoholism · doi:10.1093/alcalc/agm036 · Cited by 30 · see citing works
The Influence of Early Weaning on Aggressive Behavior in Mice
Nakamura, K., Kikusui, T., Takeuchi, Y., & Mori, Y. (2003) · Journal of Veterinary Medical Science · doi:10.1292/jvms.65.1347 · Cited by 29 · see citing works
The Ontogeny of Glucocorticoid Negative Feedback: Influence of Maternal Deprivation
van Oers, H. J. J. (1998) · Endocrinology · doi:10.1210/en.139.6.2838 · Cited by 28 · see citing works
Panzer, A. (2008) · African Journal of Psychiatry · doi:10.4314/ajpsy.v11i1.30252 · Cited by 26 · see citing works
van Heerden, J. H., Russell, V. A., Korff, A., Stein, D. J., & Illing, N. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.10.015 · Cited by 23 · see citing works
Child Maltreatment and Domestic Violence: Human Services Issues
Appel, J. K., & Kim-Appel, D. (2006) · Journal of Health and Human Services Administration · doi:10.1177/107937390602900201 · Cited by 16 · see citing works
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Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli
Cho, J. R., Treweek, J. B., Robinson, J. E., Xiao, C., Bremner, L. R., Greenbaum, A., & Gradinaru, V. (2017) · Neuron · doi:10.1016/j.neuron.2017.05.020 · Cited by 276 · see citing works
DNA methylation and childhood maltreatment: From animal models to human studies
Lutz, P.-E., & Turecki, G. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.069 · Cited by 236 · see citing works
Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis
Murphy, F., Nasa, A., Cullinane, D., Raajakesary, K., Gazzaz, A., Sooknarine, V., Haines, M., Roman, E., Kelly, L., O'Neill, A., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.748372 · Cited by 181 · see citing works
“Neglected rodent offspring have shown increased susceptibility to anxiety and depressive-like behaviors when exposed to stress in both adolescence and adulthood (145, 146).”
BackgroundMaternal separation induces neuroinflammation and long-lasting emotional alterations in mice
Gracia-Rubio, I., Moscoso-Castro, M., Pozo, O. J., Marcos, J., Nadal, R., & Valverde, O. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.09.003 · Cited by 144 · see citing works
Murthy, S., Kane, G. A., Katchur, N. J., Lara Mejia, P. S., Obiofuma, G., Buschman, T. J., McEwen, B. S., & Gould, E. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.02.021 · Cited by 118 · see citing works
Early life stress in rodents: Animal models of illness or resilience?
Murthy, S., & Gould, E. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00157 · Cited by 120 · see citing works
Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents
Murphy, M. O., Cohn, D. M., & Loria, A. S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.07.018 · Cited by 117 · see citing works
Environmental programming of susceptibility and resilience to stress in adulthood in male mice
Peña, C. J., Nestler, E. J., & Bagot, R. C. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00040 · Cited by 97 · see citing works
Ota, K. T., & Duman, R. S. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.022 · Cited by 94 · see citing works
Carlyle, B. C., Duque, A., Kitchen, R. R., Bordner, K. A., Coman, D., Doolittle, E., Papademetris, X., Hyder, F., Taylor, J. R., & Simen, A. A. (2012) · Development and Psychopathology · doi:10.1017/s095457941200079x · Cited by 80 · see citing works
Self-citationEarly life stress inhibits expression of a novel innate immune pathway in the developing hippocampus
Wei, L., Simen, A., Mane, S., & Kaffman, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.239 · Cited by 71 · see citing works
Self-citationPrenatal and early-life diesel exhaust exposure causes autism-like behavioral changes in mice
Chang, Y.-C., Cole, T. B., & Costa, L. G. (2018) · Particle and Fibre Toxicology · doi:10.1186/s12989-018-0254-4 · Cited by 65 · see citing works
Loria, A. S., Ho, D. H., & Pollock, J. S. (2014) · Acta Physiologica · doi:10.1111/apha.12189 · Cited by 53 · see citing works
“Adult and juvenile rats and mice exposed to ELS display heightened reactivity to stressors, increased anxiety as well as depression-like behaviours such as reduced anhedonia (George et al. 2010, Uchida et al. 2010, Schmidt et al. 2011).”
BackgroundBernardi, J. R., Ferreira, C. F., Senter, G., Krolow, R., de Aguiar, B. W., Portella, A. K., Kauer-Sant'Anna, M., Kapczinski, F., Dalmaz, C., Goldani, M. Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062031 · Cited by 43 · see citing works
Morris-Schaffer, K., Merrill, A., Jew, K., Wong, C., Conrad, K., Harvey, K., Marvin, E., Sobolewski, M., Oberdörster, G., Elder, A., et al. (2019) · Particle and Fibre Toxicology · doi:10.1186/s12989-019-0293-5 · Cited by 44 · see citing works
Ho, D. H., Burch, M. L., Musall, B., Musall, J. B., Hyndman, K. A., & Pollock, J. S. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00016.2016 · Cited by 34 · see citing works
Neuroanatomical changes in a mouse model of early life neglect
Duque, A., Coman, D., Carlyle, B. C., Bordner, K. A., George, E. D., Papademetris, X., Hyder, F., & Simen, A. A. (2012) · Brain Structure and Function · doi:10.1007/s00429-011-0350-9 · Cited by 28 · see citing works
Self-citationErshadi, A. S. B., Amini-Khoei, H., Hosseini, M.-J., & Dehpour, A. R. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03263-8 · Cited by 25 · see citing works
- Authors
- George, E. D., Bordner, K. A., Elwafi, H. M., & Simen, A. A.
- Affiliations
- Yale University (US)
- Corresponding author
- Simen, Arthur A
- ORCID
- Simen, Arthur A
- Venue
- BMC Neuroscience
- Published
- 2010-09-29
- Volume
- 11
- Issue
- 1
- Pages
- 123-123
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC2955691
- OpenAlex
- W2079464767
- Cited by
- 163
- References
- 97
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 10 · 2023: 8 · 2022: 14 · 2021: 15 · 2020: 17 · 2019: 12 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 11 · 2012: 5
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- Yale University
- National Institutes of Health (1s10rr019895-01)
- National Institute on Alcohol Abuse and Alcoholism (P50-AA-A06377)
- National Institute on Aging (AG030970, P01AG030004, K08AG030970)
- National Heart, Lung, and Blood Institute (T35-HL07649-22, T35HL007649)
- National Institute of Mental Health (MH 14276, T32 MH14276, T32MH014276)
- National Institute on Drug Abuse (DA022251, R03DA022251, RR19895)
- National Center for Research Resources (RR 19895, RR024138, KL2RR024138)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- maternal separation, early weaning, childhood adversity, mouse model, C57BL/6 mice, DBA/2 mice, anxiety, hyperactivity, behavioral despair, strain differences, genetic factors, mood and anxiety disorders, offspring behavior
- MeSH terms
- Aging, Animals, Anxiety, Anxiety, Separation, Behavior, Animal, Body Weight, Child, Child Abuse, Depression, Disease Models, Animal, Humans, Maternal Deprivation, Mice, Inbred C57BL, Mice, Inbred DBA, Motor Activity, Species Specificity, Swimming, Weaning, Mice
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