Skip to main content
SpringerLink
Log in

Preeclampsia as a possible risk factor for memory impairment, anxiety- and depressive-like behavior in offspring

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Preeclampsia is a condition that can affect the health in offspring at adult life. The effect on several systems has been described, but less is known about its effect on neuropsychiatric disorders at early ages.

Objective

Evaluate the possible relationship of preeclampsia with development of anxiety- and depressive-like behavior, as well as memory impairments in male and female early adolescent offspring from preeclamptic mice.

Methods

Thirty pregnant females were divided into control group receiving vehicle, and preeclampsia group receiving L-NAME in drinking water at a dose of 60 mg/Kg from day 10 of pregnancy until delivery. Offspring was weaned and sexed at 4 weeks after birth. Each group was evaluated using the elevated plus maze test (anxiety- like response), tail suspension test (depressive-like behavior) and the recognition of novel objects test (recognition memory), in addition to the open field test was performance to corroborate their motor activity and validate our results.

Results

We found that preeclampsia produces behavioral alterations in offspring, and this effect is dependent on sex. The male offspring from preeclampsia showed an enhancement in the time that mice spend in the close arms in the elevated plus maze test, and longer immobility time in the tail suspension test, compared to the offspring from healthy pregnancies. On the other hand, female offspring from preeclampsia showed a lower percentage of recognition in the memory test compared to offspring from normal pregnancy.

Conclusions

These results suggest that preeclampsia predisposes early adolescent young male offspring to develop anxiety- and depressive-like behavior as well as memory impairment in early adolescent young female offspring.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Barbie-Shoshani Y, Shoham S, Bejar C, Weinstock M (2016) Sex-specific effects of prenatal stress on memory and markers of neuronal activity in juvenile rats. Dev Neurosci 38(3). https://doi.org/10.1159/000446981

  • Bertaina-Anglade V, Enjuanes E, Morillon D, la Drieu C (2006) The object recognition task in rats and mice: a simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity. J Pharmacol Toxicol Methods 54(2). https://doi.org/10.1016/j.vascn.2006.04.001

  • Bolte AC, Van Geijn HP, Dekker GA (2001) Pathophysiology of preeclampsia and the role of serotonin. Eur J Obstet Gynecol Reproductive Biology (Vol 95(1). https://doi.org/10.1016/S0301-2115(00)00367-5

  • Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, Blakely RD, Deneris ES, Levitt P (2011) A transient placental source of serotonin for the fetal forebrain. Nature 472(7343). https://doi.org/10.1038/nature09972

  • Brust V, Schindler PM, Lewejohann L (2015) Lifetime development of behavioural phenotype in the house mouse (Mus musculus). In Frontiers in Zoology (Vol. 12, Issue 1). https://doi.org/10.1186/1742-9994-12-S1-S17

  • Cauli O, Herraiz S, Pellicer B, Pellicer A, Felipo V (2010) Treatment with sildenafil prevents impairment of learning in rats born to pre-eclamptic mothers. Neuroscience 171(2). https://doi.org/10.1016/j.neuroscience.2010.08.065

  • Cheng SW, Chou HC, Tsou KI, Fang LJ, Tsao PN (2004) Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. Early Hum Dev 76(1). https://doi.org/10.1016/j.earlhumdev.2003.10.004

  • Dachew BA, Mamun A, Maravilla JC, Alati R (2018) Pre-eclampsia and the risk of autism-spectrum disorder in offspring: Meta-analysis. Br J Psychiatry (Vol 212(3). https://doi.org/10.1192/bjp.2017.27

  • Dachew BA, Scott JG, Mamun A, Alati R (2019) Pre-eclampsia and the risk of attention-deficit/hyperactivity disorder in offspring: findings from the ALSPAC birth cohort study. Psychiatry Res 272. https://doi.org/10.1016/j.psychres.2018.12.123

  • Ding X, Yang Z, Han Y, Yu H (2015) Correlation of long-chain fatty acid oxidation with oxidative stress and inflammation in pre-eclampsia-like mouse models. Placenta 36(12). https://doi.org/10.1016/j.placenta.2015.10.014

  • Eide MG, Moster D, Irgens LM, Reichborn-Kjennerud T, Stoltenberg C, Skjærven R, Susser E, Abel K (2013) Degree of fetal growth restriction associated with schizophrenia risk in a national cohort. Psychol Med 43(10). https://doi.org/10.1017/S003329171200267X

  • Enayati M, Mosaferi B, Homberg JR, Diniz DM, Salari AA (2020) Prenatal maternal stress alters depression-related symptoms in a strain - and sex-dependent manner in rodent offspring. Life Sciences, 251. https://doi.org/10.1016/j.lfs.2020.117597

  • Fajersztajn L, Veras MM (2017) Hypoxia: From Placental Development to Fetal Programming. In Birth Defects Research (Vol. 109, Issue 17). https://doi.org/10.1002/bdr2.1142

  • Fraser A, Nelson SM, MacDonald-Wallis C, Sattar N, Lawlor DA (2013) Hypertensive disorders of pregnancy and cardiometabolic health in adolescent offspring. Hypertension 62(3). https://doi.org/10.1161/HYPERTENSIONAHA.113.01513

  • Galbally M, Watson SJ, Lappas M, de Kloet ER, Wyrwoll CS, Mark PJ, Lewis AJ (2022) Exploring sex differences in fetal programming for childhood emotional disorders. Psychoneuroendocrinology, 141. https://doi.org/10.1016/j.psyneuen.2022.105764

  • Gumusoglu SB, Chilukuri ASS, Hing BWQ, Scroggins SM, Kundu S, Sandgren JA, Santillan MK, Santillan DA, Grobe JL, Stevens HE (2021) Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model. Translational Psychiatry 11(1). https://doi.org/10.1038/s41398-021-01205-0

  • Heikura U, Hartikainen AL, Nordström T, Pouta A, Taanila A, Järvelin MR (2013) Maternal hypertensive disorders during pregnancy and mild cognitive limitations in the offspring. Paediatr Perinat Epidemiol 27(2). https://doi.org/10.1111/ppe.12028

  • Ianosi-Irimie M, Vu HV, Whitbred JM, Pridjian CA Nadig, J. D., Williams MY, Wrenn DC, Pridjian G, Puschett, Puschett JB (2005) A rat model of Preeclampsia. Clin Exp Hypertens 27(8):605–617. https://doi.org/10.1080/10641960500298608

  • Kajantie E, Eriksson JG, Osmond O, Thornburg K, Barker DJP (2009) Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke 40(4):1176–1180

    Article  PubMed  Google Scholar 

  • Kay VR, Rätsep MT, Figueiró-Filho EA, Croy BA (2019) Preeclampsia may influence offspring neuroanatomy and cognitive function: A role for placental growth factor†. In Biology of Reproduction (Vol. 101, Issue 2). https://doi.org/10.1093/biolre/ioz095

  • Kay VR, Rätsep MT, Cahill LS, Hickman AF, Zavan B Newport, ME, Ellegood J, Laliberte CL, Reynolds JN, Carmeliet P, Tayade C, Sled JG, Croy BA (2018) Effects of placental growth factor deficiency on behavior, neuroanatomy, and cerebrovasculature of mice. Physiol Genom 50(10). https://doi.org/10.1152/physiolgenomics.00076.2018

  • Laloux C, Mairesse J, Van Camp G, Giovine A, Branchi I, Bouret S, Morley-Fletcher S, Bergonzelli G, Malagodi M, Gradini R, Nicoletti F, Darnaudéry M, Maccari S (2012) Anxiety-like behaviour and associated neurochemical and endocrinological alterations in male pups exposed to prenatal stress. Psychoneuroendocrinology 37(10). https://doi.org/10.1016/j.psyneuen.2012.02.010

  • Laviola G, Macrì S, Morley-Fletcher S, Adriani W (2003) Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence. Neurosci Biobehav Rev 27(1–2). https://doi.org/10.1016/S0149-7634(03)00006-X

  • Liu X, Zhao W, Liu H, Kang Y, Ye C, Gu W, Hu R, Li X (2016) Developmental and functional brain impairment in offspring from Preeclampsia-Like rats. Mol Neurobiol 53(2). https://doi.org/10.1007/s12035-014-9060-7

  • Liu L, Lin Z, Zheng B, Wang L, Zou J, Wu S, Jiang Z, Jin Q, Lai X, Lin P (2020) Reduced intellectual ability in offspring born from preeclamptic mothers: A prospective cohort study. Risk Management and Healthcare Policy, 13. https://doi.org/10.2147/RMHP.S277521

  • Longtine MS, Nelson DM (2011) Placental dysfunction and fetal programming: the importance of placental size, shape, histopathology, and molecular composition. Semin Reprod Med 29(3). https://doi.org/10.1055/s-0031-1275515

  • Lu SF, Lin QF, Li Y, Jiang XJ (2019) Synthesis of nomega-Nitro-L-arginine methyl ester modified reduced graphene oxide nanosheets and their protective action on experimental preeclampsia in mice. J Photochem Photobiol B 194. https://doi.org/10.1016/j.jphotobiol.2019.03.013

  • Maher GM, Dalman C, O’Keeffe GW, Kearney PM, McCarthy FP, Kenny LC, Khashan AS (2020) Association between preeclampsia and attention-deficit hyperactivity disorder: a population-based and sibling-matched cohort study. Acta Psychiatrica Scandinavica 142(4). https://doi.org/10.1111/acps.13162

  • Mann JR, McDermott S, Bao H, Hardin J, Gregg A (2010) Pre-eclampsia, birth weight, and autism spectrum disorders. J Autism Dev Disord 40(5). https://doi.org/10.1007/s10803-009-0903-4

  • Motta C, Grosso C, Zanuzzi C, Molinero D, Picco N, Bellingeri R, Alustiza F, Barbeito C, Vivas A, Romanini MC (2015) Effect of Sildenafil on Pre-eclampsia-like Mouse Model Induced by L-Name. Reprod Domest Anim 50(4). https://doi.org/10.1111/rda.12536

  • Moura CA, Oliveira MC, Costa LF, Tiago PRF, Holanda VAD, Lima RH, Cagni FC, Lobão-Soares B, Bolaños-Jiménez F, Gavioli EC (2020) Prenatal Restraint stress impairs Recognition Memory in Adult Male and female offspring. Acta Neuropsychiatrica. https://doi.org/10.1017/neu.2020.3

    Article  PubMed  Google Scholar 

  • Phipps EA, Thadhani R, Benzing T, Karumanchi SA (2019) Pre-eclampsia: pathogenesis, novel diagnostics and therapies. In Nature Reviews Nephrology (Vol. 15, Issue 5). https://doi.org/10.1038/s41581-019-0119-6

  • Ramírez-Vélez R (2012) Programación Fetal in utero y su impacto en la salud del adulto. In Endocrinologia y Nutricion (Vol. 59, Issue 6). https://doi.org/10.1016/j.endonu.2012.02.002

  • Rätsep MT, Hickman AF, Maser B, Pudwell J, Smith GN, Brien D, Stroman PW, Adams MA, Reynolds JN, Croy BA, Paolozza A (2016) Impact of preeclampsia on cognitive function in the offspring. Behavioural Brain Research, 302. https://doi.org/10.1016/j.bbr.2016.01.030

  • Reynolds LP, Borowicz PP, Caton JS, Crouse MS, Dahlen CR, Ward AK (2019) Developmental Programming of Fetal Growth and Development. In Veterinary Clinics of North America - Food Animal Practice (Vol. 35, Issue 2). https://doi.org/10.1016/j.cvfa.2019.02.006

  • Rosa MJ, Nentin F, Bosquet Enlow M, Hacker MR, Pollas N, Coull B, Wright RJ (2019) Sex-specific associations between prenatal negative life events and birth outcomes. Stress 22(6). https://doi.org/10.1080/10253890.2019.1608944

  • Salari AA, Fatehi-Gharehlar L, Motayagheni N, Homberg JR (2016) Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring. Behav Brain Res 311. https://doi.org/10.1016/j.bbr.2016.05.062

  • Shah R, Courtiol E, Castellanos FX, Teixeira CM (2018) Abnormal serotonin levels during perinatal development lead to behavioral deficits in adulthood. Front Behav Neurosci 12. https://doi.org/10.3389/fnbeh.2018.00114

  • Silva D, Colvin L, Hagemann E, Bower C (2014) Environmental risk factors by gender associated with attention-deficit/ hyperactivity disorder. Pediatrics 133(1). https://doi.org/10.1542/peds.2013-1434

  • Sørensen HJ, Mortensen EL, Reinisch JM, Mednick SA (2003) Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring? Am J Psychiatry 160(3). https://doi.org/10.1176/appi.ajp.160.3.464

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85(3). https://doi.org/10.1007/BF00428203

  • Stevenson K, Lillycrop KA, Silver MJ (2020) Fetal programming and epigenetics. In Current Opinion in Endocrine and Metabolic Research (Vol. 13). https://doi.org/10.1016/j.coemr.2020.07.005

  • Sverrisson FA, Bateman BT, Aspelund T, Skulason S, Zoega H (2018) Preeclampsia and academic performance in children: a nationwide study from Iceland. PLoS ONE 13(11). https://doi.org/10.1371/journal.pone.0207884

  • Tuovinen S, Aalto-Viljakainen T, Eriksson JG, Kajantie E, Lahti J, Pesonen AK, Heinonen K, Lahti M, Osmond C, Barker DJP, Räikkönen K (2014) Maternal hypertensive disorders during pregnancy: adaptive functioning and psychiatric and psychological problems of the older offspring. BJOG: Int J Obstet Gynecol 121(12). https://doi.org/10.1111/1471-0528.12753

  • Van den Hove DLA, Leibold NK, Strackx E, Martinez-Claros M, Lesch KP, Steinbusch HWM, Schruers KRJ, Prickaerts J (2014) Prenatal stress and subsequent exposure to chronic mild stress in rats; interdependent effects on emotional behavior and the serotonergic system. Eur Neuropsychopharmacol 24(4). https://doi.org/10.1016/j.euroneuro.2013.09.006

  • Walf AA, Frye CA (2007) The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc 2(2). https://doi.org/10.1038/nprot.2007.44

  • Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I (2015) Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr 169(2). https://doi.org/10.1001/jamapediatrics.2014.2645

  • Zuena AR, Mairesse J, Casolini P, Cinque C, Alemà GS, Morley-Fletcher S, Chiodi V, Spagnoli LG, Gradini R, Catalani A, Nicoletti F, Maccari S (2008) Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats. PLoS ONE 3(5). https://doi.org/10.1371/journal.pone.0002170

Download references

Acknowledgements

The authors would like to thank to Beatriz Cruz Lopez for her excellent technical assistance. We acknowledge Mrs. Gena Ingelido’s help for her excellent assistance in English language revision. This study was supported by projects SIP-Instituto Politécnico Nacional, México (20230781 and 20231264) and Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, México.

Author information

Authors and Affiliations

  1. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Santo Tomás, Ciudad de México, C.P. 11340, México

    Blanca Rubí Vélez-Godínez, Pedro López-Sánchez & Nayeli Páez-Martínez

  2. Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría “Ramón de la Fuente Muñiz”, Ciudad de México, México

    Nayeli Páez-Martínez

Authors
  1. Blanca Rubí Vélez-Godínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pedro López-Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nayeli Páez-Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nayeli Páez-Martínez.

Ethics declarations

Competing interest

Not applicable.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vélez-Godínez, B.R., López-Sánchez, P. & Páez-Martínez, N. Preeclampsia as a possible risk factor for memory impairment, anxiety- and depressive-like behavior in offspring. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06568-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00213-024-06568-y

Keywords

Search

Navigation