Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

Rayen, Ine; Gemmel, Mary; Pauley, Grace; Steinbusch, Harry W.M.; Pawluski, Jodi L.

doi:10.1007/s00213-014-3758-0

Cited by 56 publications

(69 citation statements)

References 102 publications

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“…Maternal postpartum fluoxetine increased density of doublecortin-expressing cells in the dorsal dentate gyrus in adult male offspring. This is at least partially consistent with a prior study which showed that maternal postpartum fluoxetine slightly increased density of doublecortin-expressing cells in adult male offspring and decreased it in the adult female offspring (Rayen et al, 2015). However, our results suggest that after behavioral testing, maternal postpartum fluoxetine stimulates doublecortin expression in the dorsal (but not ventral) dentate gyrus, and only in the adult male offspring.…”

Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated supporting

confidence: 87%

“…This study used a higher dose of fluoxetine (10 mg/kg) than Rayen et al, 2015 (5 mg/kg). Regardless, maternal fluoxetine appears to increase doublecortin expression in adult males although this may be mitigated by prenatal stress (Rayen et al, 2015), but not by maternal postpartum CORT. Indeed, the increase in immature neurons due to maternal fluoxetine was only evident in the male offspring of CORT-treated dams.…”

Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated mentioning

confidence: 75%

“…Maternal postpartum fluoxetine reversed the detrimental effects of prenatal stress on hippocampal doublecortin expression in both male and female adolescent rat offspring (Rayen et al, 2011). However, by adulthood, maternal postpartum fluoxetine only diminished doublecortin expression after prenatal stress exposure, particularly in adult male offspring (Rayen et al, 2015). Thus, hippocampal neurogenesis represents a neurobiological intersection of developmental exposure to stress, antidepressants, and adult behavioral outcomes and will be investigated in the present study.…”

Section: Introductionmentioning

confidence: 86%

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Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

et al. 2016

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Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations.

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Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated supporting

confidence: 87%

Section: Maternal Postpartum Fluoxetine Increased Serotonin-mediated mentioning

confidence: 75%

Section: Introductionmentioning

confidence: 86%

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Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

et al. 2016

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“…Treating dams with FLX in the postpartum reversed the suppressive effect of prenatal stress on hippocampal DCX-expressing cells in both adolescent male and female offspring [17]. However, this interaction between prenatal stress and postpartum FLX exposure did not persist to adulthood as maternal postpartum FLX decreased number of DCX-expressing cells in offspring also exposed to prenatal stress, particularly in the males [29]. We recently reported that FLX given to the dam during the postpartum period increased density of DCX-expressing cells in the dorsal hippocampus of adult male offspring but not in adult female offspring [12].…”

Section: Introductionmentioning

confidence: 99%

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

et al. 2017

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BackgroundPostpartum depression affects approximately 15% of mothers and represents a form of early life adversity for developing offspring. Postpartum depression can be treated with prescription antidepressants like fluoxetine (FLX). However, FLX can remain active in breast milk, raising concerns about the consequences of neonatal FLX exposure. The hippocampus is highly sensitive to developmental stress, and males and females respond differently to stress at many endpoints, including hippocampal plasticity. However, it is unclear how developmental exposure to FLX alters the trajectory of hippocampal development. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum depression) and concurrent FLX on hippocampal neurogenesis in male and female offspring.MethodsFemale Sprague-Dawley rat dams were treated daily with either CORT or oil and FLX or saline from postpartum days 2–23. Offspring were perfused on postnatal day 31 (pre-adolescent), postnatal day 42 (adolescent), and postnatal day 69 (adult). Tissue was processed for doublecortin (DCX), an endogenous marker of immature neurons, in the dorsal and ventral hippocampus.ResultsMaternal postpartum CORT reduced density of DCX-expressing cells in the dorsal hippocampus of pre-adolescent males and increased it in adolescent males, suggesting that postpartum CORT exposure disrupted the typical progression of the density of DCX-expressing cells. Further, among offspring of oil-treated dams, pre-adolescent males had greater density of DCX-expressing cells than pre-adolescent females, and maternal postpartum CORT prevented this sex difference. In pre-adolescent females, maternal postpartum FLX decreased the density of DCX-expressing cells in the dorsal hippocampus compared to saline. As expected, maternal CORT reduced the density of DCX-expressing cells in adult female, but not male, offspring. The combination of maternal postpartum CORT/FLX diminished density of DCX-expressing cells in dorsal hippocampus regardless of sex or age.ConclusionsThese findings reveal how modeling treatment of postpartum depression with FLX alters hippocampal neurogenesis in developing offspring differently depending on sex, predominantly in the dorsal dentate gyrus and earlier in life.

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“…Other studies found that depression reduces neuronal plasticity and impairs synaptic function, which may be an important target of pharmacological intervention (39). The anti-psychotic drug Lurasidone has shown to be effective in a CMS model through the modulation of synaptic and neuroplastic proteins and PSD-95 (40).…”

Section: Discussionmentioning

confidence: 99%

Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

Zhao

Liang

et al. 2017

Experimental and Therapeutic Medicine

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Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups). The MC group and the three JYCF groups were subjected to 3 weeks of unpredictable chronic mild stress (UCMS) to induce depression-like behavior. All groups were subjected to a sucrose consumption test along with a forced swimming test to confirm depression-like behavior, an open-field test and an elevated plus maze test to confirm anxiety-like behavior, and a Morris water maze test to evaluate spatial learning and memory. In addition, synaptic density in the hippocampus was evaluated and western blot and immunostaining were used to analyze hippocampal expression of postsynaptic density protein-95 (PSD95), synaptophysin (Syn), cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt and glycogen synthase kinase (GSK)-3β as well as their phosphorylated (p) versions. The results showed that JYCF (2.5 and 5 g/kg) alleviated depressive-like behaviors and increased synaptic density in UCMS mice. Moreover, JYCF upregulated the expression of PSD95, Syn and BDNF and increased phosphorylated Akt, CREB and GSK-3β in the hippocampus. These results suggested that JYCF exerts an anti-depressant-like activity in UCMS-induced mice, which is likely to be mediated by reversing the stress-induced disruption of BDNF and GSK-3β activity.

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Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity

Abstract: There are long-term effects of developmental SSRI exposure on hippocampal plasticity that is differentially affected by expose to maternal adversity and offspring sex.

Cited by 56 publications

References 102 publications

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis

Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development

Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

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