Opposite Effects of Early Maternal Deprivation on Neurogenesis in Male Versus Female Rats

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Jan 31

PMID 19180242

Citations 74

Authors

Charlotte A Oomen

Carlos E N Girardi

Rudy Cahyadi

Eva C Verbeek

Harm Krugers

Marian Joels

Paul J Lucassen

Affiliations

Soon will be listed here.

Abstract

Background: Major depression is more prevalent in women than in men. The underlying neurobiological mechanisms are not well understood, but recent data shows that hippocampal volume reductions in depressed women occur only when depression is preceded by an early life stressor. This underlines the potential importance of early life stress, at least in women, for the vulnerability to develop depression. Perinatal stress exposure in rodents affects critical periods of brain development that persistently alter structural, emotional and neuroendocrine parameters in adult offspring. Moreover, stress inhibits adult hippocampal neurogenesis, a form of structural plasticity that has been implicated a.o. in antidepressant action and is highly abundant early postnatally. We here tested the hypothesis that early life stress differentially affects hippocampal structural plasticity in female versus male offspring.

Principal Findings: We show that 24 h of maternal deprivation (MD) at PND3 affects hippocampal structural plasticity at PND21 in a sex-dependent manner. Neurogenesis was significantly increased in male but decreased in female offspring after MD. Since no other structural changes were found in granule cell layer volume, newborn cell survival or proliferation rate, astrocyte number or gliogenesis, this indicates that MD elicits specific changes in subsets of differentiating cells and differentially affects immature neurons. The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care.

Conclusions: Our data shows that early environment has a critical influence on establishing sex differences in neural plasticity and supports the concept that the setpoint for neurogenesis may be determined during perinatal life. It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.

Citing Articles

FKBP51 in glutamatergic forebrain neurons promotes early life stress inoculation in female mice.

van Doeselaar L, Abromeit A, Stark T, Menegaz D, Ballmann M, Mitra S Nat Commun. 2025; 16(1):2529.

PMID: 40087272 DOI: 10.1038/s41467-025-57952-x.

Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age.

Sanguino-Gomez J, Krugers H Neurobiol Stress. 2024; 31:100636.

PMID: 38883213 PMC: 11177066. DOI: 10.1016/j.ynstr.2024.100636.

Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.

Geertsema J, Kratochvil M, Gonzalez-Dominguez R, Lefevre-Arbogast S, Low D, Du Preez A Neurobiol Stress. 2024; 31:100641.

PMID: 38827176 PMC: 11140806. DOI: 10.1016/j.ynstr.2024.100641.

Neurobiological mechanisms involved in maternal deprivation-induced behaviours relevant to psychiatric disorders.

Zanta N, Assad N, Suchecki D Front Mol Neurosci. 2023; 16:1099284.

PMID: 37122626 PMC: 10133561. DOI: 10.3389/fnmol.2023.1099284.

Early life adversity impaired dorsal striatal synaptic transmission and behavioral adaptability to appropriate action selection in a sex-dependent manner.

de Carvalho G, Khoja S, Haile M, Chen L Front Synaptic Neurosci. 2023; 15:1128640.

PMID: 37091877 PMC: 10116150. DOI: 10.3389/fnsyn.2023.1128640.

References

Lemaire V, Koehl M, Le Moal M, Abrous D . Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci U S A. 2000; 97(20):11032-7. PMC: 27143. DOI: 10.1073/pnas.97.20.11032. View

Desbonnet L, Garrett L, Daly E, McDermott K, Dinan T . Sexually dimorphic effects of maternal separation stress on corticotrophin-releasing factor and vasopressin systems in the adult rat brain. Int J Dev Neurosci. 2008; 26(3-4):259-68. DOI: 10.1016/j.ijdevneu.2008.02.004. View

Schmidt-Hieber C, Jonas P, Bischofberger J . Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature. 2004; 429(6988):184-7. DOI: 10.1038/nature02553. View

Walker C, Perrin M, Vale W, Rivier C . Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus. Endocrinology. 1986; 118(4):1445-51. DOI: 10.1210/endo-118-4-1445. View

Dranovsky A, Hen R . Hippocampal neurogenesis: regulation by stress and antidepressants. Biol Psychiatry. 2006; 59(12):1136-43. PMC: 7537828. DOI: 10.1016/j.biopsych.2006.03.082. View

Darnaudery M, Maccari S . Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev. 2008; 57(2):571-85. DOI: 10.1016/j.brainresrev.2007.11.004. View

Galea L . Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Res Rev. 2007; 57(2):332-41. DOI: 10.1016/j.brainresrev.2007.05.008. View

Dobrossy M, Drapeau E, Aurousseau C, Le Moal M, Piazza P, Abrous D . Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date. Mol Psychiatry. 2003; 8(12):974-82. DOI: 10.1038/sj.mp.4001419. View

Garcia-Segura L, Suarez I, Segovia S, Tranque P, Cales J, Aguilera P . The distribution of glial fibrillary acidic protein in the adult rat brain is influenced by the neonatal levels of sex steroids. Brain Res. 1988; 456(2):357-63. DOI: 10.1016/0006-8993(88)90239-9. View

10.

Thomas R, Urban J, Peterson D . Acute exposure to predator odor elicits a robust increase in corticosterone and a decrease in activity without altering proliferation in the adult rat hippocampus. Exp Neurol. 2006; 201(2):308-15. DOI: 10.1016/j.expneurol.2006.04.010. View

11.

Weiss E, Longhurst J, Mazure C . Childhood sexual abuse as a risk factor for depression in women: psychosocial and neurobiological correlates. Am J Psychiatry. 1999; 156(6):816-28. DOI: 10.1176/ajp.156.6.816. View

12.

Heine V, Maslam S, Zareno J, Joels M, Lucassen P . Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. Eur J Neurosci. 2004; 19(1):131-44. DOI: 10.1046/j.1460-9568.2003.03100.x. View

13.

Llorente R, Llorente-Berzal A, Petrosino S, Marco E, Guaza C, Prada C . Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system. Dev Neurobiol. 2008; 68(11):1334-47. DOI: 10.1002/dneu.20666. View

14.

Plotsky P, Thrivikraman K, Nemeroff C, Caldji C, Sharma S, Meaney M . Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology. 2005; 30(12):2192-204. DOI: 10.1038/sj.npp.1300769. View

15.

Kole M, Czeh B, Fuchs E . Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress. Hippocampus. 2004; 14(6):742-51. DOI: 10.1002/hipo.10212. View

16.

Barbazanges A, Piazza P, Le Moal M, Maccari S . Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci. 1996; 16(12):3943-9. PMC: 6578602. View

17.

Banasr M, Soumier A, Hery M, Mocaer E, Daszuta A . Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis. Biol Psychiatry. 2006; 59(11):1087-96. DOI: 10.1016/j.biopsych.2005.11.025. View

18.

Tauber S, Bunkowski S, Schlumbohm C, Ruhlmann M, Fuchs E, Nau R . No long-term effect two years after intrauterine exposure to dexamethasone on dentate gyrus volume, neuronal proliferation and differentiation in common marmoset monkeys. Brain Pathol. 2008; 18(4):497-503. PMC: 8095542. DOI: 10.1111/j.1750-3639.2008.00149.x. View

19.

Nacher J, Gomez-Climent M, McEwen B . Chronic non-invasive glucocorticoid administration decreases polysialylated neural cell adhesion molecule expression in the adult rat dentate gyrus. Neurosci Lett. 2004; 370(1):40-4. DOI: 10.1016/j.neulet.2004.07.062. View

20.

Heine V, Maslam S, Joels M, Lucassen P . Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation. Neurobiol Aging. 2004; 25(3):361-75. DOI: 10.1016/S0197-4580(03)00090-3. View