Effects of prenatal stress and neonatal handling on anxiety, spatial learning and serotonergic system of male offspring mice

Akatsu, Shigemi; Ishikawa, Chihiro; Takemura, Kaori; Ohtani, Akiko; Shiga, Takashi

doi:10.1016/j.neures.2015.07.002

Cited by 60 publications

(61 citation statements)

References 58 publications

(50 reference statements)

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“…The water was made opaque by non-toxic white tempura paint. The pool was located in a room rich with distal cues, which remained unobstructed throughout the duration of the experiment [53]. During all hidden platform trials, the platform was submerged ~1.0 cm under the surface of the water.…”

Section: Methodsmentioning

confidence: 99%

Corticosterone response to gestational stress and postpartum memory function in mice

et al. 2017

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Maternal stress is a common adversity during pregnancy. Gestational corticosterone alternations are thought to contribute to the etiology of postpartum behavioral disturbances. However, the impact of stress during pregnancy, in particular noise exposure, on gestational corticosterone fluctuations and spatial cognition in postpartum mice has not been fully understood yet. We hypothesized that noise exposure during pregnancy negatively affects gestational corticosterone levels and postpartum memory function in the dams similar to the physical stressors. Pregnant C57BL/6 mice were randomly assigned to either one of two stress conditions or a control condition. The noise stress (NS) was induced by presenting a loud intermittent 3000 Hz frequency on gestational days (GDs) 12, 14, and 16 for 24 hours, whereas the physical stress (PS) consisted of restraint and exposure to an elevated platform on GDs 12–16. Plasma corticosterone level was collected on GDs 11 and 17, and Morris water task (MWT) was carried out 30 days after parturition. Compared to the control group, the level of corticosterone in the stressed groups was significantly increased on GD17 relative to GD11. Significantly longer swim time and lower swim speed were observed in both stressed groups relative to the control group. Probe time was significantly shorter in the NS group than the other groups. The delta corticosterone level was significantly correlated with the swim time as well as the probe time in the three groups. Given the results, the adverse effects of gestational noise exposure on the hypothalamic pituitary-adrenal (HPA) axis activation and postpartum spatial learning and memory function were as large as/ or a bit stronger than the physical stresses. The findings suggest the significance of conservation against loud noise exposure in daily living, as well as need to further notice to the different aspects of gestational stress in mothers’ behavior like offspring.

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Section: Methodsmentioning

confidence: 99%

Corticosterone response to gestational stress and postpartum memory function in mice

et al. 2017

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“…Real-time reverse transcription PCR was performed as previously described [26]. In brief, each brain region was homogenized in RNAiso (Takara) on ice using a sonicator (Taitec).…”

Section: Methodsmentioning

confidence: 99%

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

Ishikawa

Ogura

et al. 2017

PLoS ONE

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Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear’s vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes.

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“…In animal models, research has linked prenatal stress to heightened levels of anxiety, decreased sociability, and deficits in cognitive and motor function (Akatsu et al, 2015; Said et al, 2015). Despite evidence for such phenotypes, the mechanisms by which maternal stress alters offspring neural function are largely unknown.…”

Section: Introductionmentioning

confidence: 99%

The role of IL-6 in neurodevelopment after prenatal stress

Gumusoglu

Fine

Murray

et al. 2017

Brain, Behavior, and Immunity

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Prenatal stress exposure is associated with adverse psychiatric outcomes, including autism and ADHD, as well as locomotor and social inhibition and anxiety-like behaviors in animal offspring. Similarly, maternal immune activation also contributes to psychiatric risk and aberrant offspring behavior. The mechanisms underlying these outcomes are not clear. Offspring microglia and the pro-inflammatory cytokine interleukin-6 (IL-6), known to influence microglia, may serve as common mechanisms between prenatal stress and prenatal immune activation. To evaluate the role of prenatal IL-6 in prenatal stress, microglia morphological analyses were conducted at embryonic days 14 (E14), E15, and in adult mice. Offspring microglia and behavior were evaluated after repetitive maternal restraint stress, repetitive maternal IL-6, or maternal IL-6 blockade during stress from E12 onwards. At E14, novel changes in cortical plate embryonic microglia were documented—a greater density of the mutivacuolated morphology. This resulted from either prenatal stress or IL-6 exposure and was prevented by IL-6 blockade during prenatal stress. Prenatal stress also resulted in increased microglia ramification in adult brain, as has been previously shown. As with embryonic microglia, prenatal IL-6 recapitulated prenatal stress-induced changes in adult microglia. Furthermore, prenatal IL-6 was able to recapitulate the delay in GABAergic progenitor migration caused by prenatal stress. However, IL-6 mechanisms were not necessary for this delay which persisted after prenatal stress despite IL-6 blockade. As we have previously demonstrated, behavioral effects of prenatal stress in offspring, including increased anxiety-like behavior, decreased sociability, and locomotor inhibition, may be related to these GABAergic delays. While adult microglia changes were ameliorated by IL-6 blockade, these behavioral changes were independent of IL-6 mechanisms, similar to GABAergic delays. This and previous work from our laboratory suggest multiple mechanisms, including GABAergic delays, may underlie prenatal stress-linked deficits.

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Effects of prenatal stress and neonatal handling on anxiety, spatial learning and serotonergic system of male offspring mice

Cited by 60 publications

References 58 publications

Corticosterone response to gestational stress and postpartum memory function in mice

Corticosterone response to gestational stress and postpartum memory function in mice

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

The role of IL-6 in neurodevelopment after prenatal stress

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