Developmental and behavioral consequences of early life maternal separation stress in a mouse model of fetal alcohol spectrum disorder

Alberry, Bonnie; Singh, Shiva M.

doi:10.1016/j.bbr.2016.04.031

Cited by 23 publications

(29 citation statements)

References 57 publications

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“…However, despite being correlational, here we present compelling evidence that PAE animals do not respond in the same way as controls to early-life adversity. Moreover, there are very few clinical and preclinical studies that investigate the dynamic and overlapping effects of PAE and early-life adversity (Alberry and Singh, 2016; Price et al, 2017) and the current study starts to fill this gap in the literature by laying the groundwork for future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, consistent findings indicate that early postnatal adversity such as neglect, abuse, and/or maltreatment – especially from the caregiver – can also change brain development and have long-lasting consequences for the physical and mental health of the offspring (Chen and Baram, 2016; Cirulli et al, 2009; Danese and McEwen, 2012; Drury et al, 2016; Heim et al, 2010; McEwen, 2008; Raineki et al, 2012; Teicher et el., 2003). Nevertheless, relatively few studies have investigated how exposure to adverse and/or stressful environments early in postnatal life contributes to the pervasive and long-lasting negative effects of PAE (Alberry and Singh, 2016; Price et al, 2017). …”

Section: Introductionmentioning

confidence: 99%

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Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

Raineki

Holman

Baglot

et al. 2017

Brain, Behavior, and Immunity

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The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8–12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

Raineki

Holman

Baglot

et al. 2017

Brain, Behavior, and Immunity

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“…In order to assess possible effects of drug treatment on spontaneous locomotor activity, the animals were submitted to the open field paradigm as previously described 37 . Briefly, the open field area (50 × 50 × 50 cm) with a video camera attached to a computer was used to record animal behaviors, measured using EthoVision XT 11 software.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion

Wang

et al. 2017

Sci Rep

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Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl2 dosage, intracellular Ca2+ increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.

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“…Females (10 weeks old) were housed individually and randomly assigned to ethanol or control groups. Both groups had free access to water, with the ethanol group additionally provided free access to 10% ethanol in water solution (Kleiber et al, 2011;Alberry and Singh, 2016). Ethanol was introduced with increasing concentrations of 2%, 5%, and 10% after 48 h with the previous concentration.…”

Section: Continuous Preference Drinking Modelmentioning

confidence: 99%

“…Postnatal maternal separation and isolation were used to induce early life stress, as described previously (Savignac et al, 2011;Benner et al, 2014;Alberry and Singh, 2016). On postnatal day 2, half of each litter was randomly selected for stress, tail coloring with permanent marker was used to distinguish pups.…”

Section: Early Life Stress Via Maternal Separation and Isolationmentioning

confidence: 99%

Hippocampal DNA Methylation in a Mouse Model of Fetal Alcohol Spectrum Disorder That Includes Maternal Separation Stress Only Partially Explains Changes in Gene Expression

Alberry

Singh

2020

Front. Genet.

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Fetal alcohol spectrum disorder (FASD) is characterized by developmental and behavioral deficits caused by maternal drinking during pregnancy. Children born with FASD often face additional stresses, including maternal separation, that add yet additional deficits. The mechanism associated with this interaction is not known. We have used a mouse model for prenatal ethanol exposure and maternal separation to demonstrate that the combination of the two treatments results in more than additive deficits. Furthermore, the behavioral deficits are associated with changes in hippocampal gene expression that persist into adulthood. What initiates and maintains these changes remains to be established and forms the focus of this report. Specifically, MeDIP-Seq was used to assess if changes in promoter DNA methylation are affected by exposure to prenatal ethanol and maternal separation including its relationship to gene expression. The novel results show that different sets of genes implicated by promoter DNA methylation are affected by both treatments independently, and a relatively unique set of genes are affected by the combination of the two treatments. Prenatal ethanol exposure leads to altered promoter DNA methylation at genes important for transcriptional regulation. Maternal separation leads to changes at genes important for histone methylation and immune response, and the combination of two treatments results in DNA methylation changes at genes important for neuronal migration and immune response. Our dual results from the same hippocampal samples suggest there is minimal complementarity between changes in promoter DNA methylation and gene expression, although genes involved tend to be critical for brain development and function. While remaining to be validated, such results argue that mechanisms beyond promoter DNA methylation must be involved in lasting gene expression alterations leading to behavioral deficits implicated in FASD. They may facilitate early and reliable diagnosis, as well as novel strategies for the amelioration of FASD-related deficits.

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Developmental and behavioral consequences of early life maternal separation stress in a mouse model of fetal alcohol spectrum disorder

Cited by 23 publications

References 57 publications

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion

Hippocampal DNA Methylation in a Mouse Model of Fetal Alcohol Spectrum Disorder That Includes Maternal Separation Stress Only Partially Explains Changes in Gene Expression

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