Effects of Prenatal Cocaine Exposure on Social Development in Mice

Kabir, Zeeba D.; Kennedy, Bruce C.; Katzman, Aaron; Lahvis, Garet P.; Kosofsky, Barry E.

doi:10.1159/000360524

Cited by 12 publications

(18 citation statements)

References 48 publications

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“…We also found a trend toward lower USV production, suggesting a relationship between social investigation and USV production that we have noted previously [80, 81]. Effects of DA on adolescent social investigation by B6 mice are modest in the current report and are similar to our previous studies with FVB mice [65].…”

Section: Discussionsupporting

confidence: 90%

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Mills

Pearce

Khan

et al. 2016

Behavioural Brain Research

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Domoic acid (DA) is a toxin produced by marine algae and known primarily for its role in isolated outbreaks of Amnestic Shellfish Poisoning and for the damage it inflicts on marine mammals, particularly California sea lions. Lethal effects of DA are often preceded by seizures and coma. Exposure to DA during development can result in subtle and highly persistent effects on brain development and include behavioral changes that resemble diagnostic features of schizophrenia and anomalies in social behavior we believe are relevant to autism spectrum disorder (ASD). To more fully examine this hypothesis, we chose to examine adolescent mice exposed in utero to DA for endpoints relevant to ASD, specifically changes in social behavior and network structure, the latter measured by resting state functional connectivity (rsfcMRI). We found that male offspring exposed in utero to DA expressed reproducible declines in social interaction and atypical patterns of functional connectivity in the anterior cingulate, a region of the default mode network that is critical for social functioning. We also found disruptions in global topology in regions involved in the processing of reward, social, and sensory experiences. Finally, we found that DA exposed males expressed a pattern of local over-connectivity. These anomalies in brain connectivity bear resemblance to connectivity patterns in ASD and help validate DA-exposed mice as a model of this mental disability.

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Section: Discussionsupporting

confidence: 90%

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Mills

Pearce

Khan

et al. 2016

Behavioural Brain Research

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“…Therefore, BDNFTrKB signaling in the frontal cortex became a highly justifiable choice for the present study. Overall, our finding of increased BDNF-TrkB signaling in the frontal cortex is consistent with earlier reports [13,16] . However, our findings offer novel evidence to advance the field by illustrating the role of developmental stage and sex in mediating the effects of cocaine exposure, and also by demonstrating an epigenetic mechanism underlying the increases in frontal cortical BDNF levels.…”

Section: Discussionsupporting

confidence: 93%

“…However, earlier reports showed that neither BDNF nor TrkB expression was altered in the medial prefrontal cortex of prenatally cocaine-exposed adult mice [16] . Therefore, the increased BDNF signaling observed in the present study is likely selective to the dorsal prefrontal cortex.…”

Section: Discussionmentioning

confidence: 85%

Prenatal Cocaine Exposure Alters BDNF-TrkB Signaling in the Embryonic and Adult Brain

McCarthy

Mueller²,

Cannon³

et al. 2016

Dev Neurosci

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Prenatal cocaine exposure remains a major public health concern because of its adverse effects on cognitive function. Although the molecular mechanisms underlying the cognitive impairment are not fully understood, brain-derived neurotrophic factor (BDNF) signaling via its receptor tyrosine kinase B (TrkB) is emerging as a potential candidate. We used a mouse model to examine the impact of ongoing cocaine exposure on BDNF expression in the dorsal forebrain on embryonic day 15 (E15) as well as the long-term effects of prenatal cocaine exposure on BDNF-TrkB signaling in the frontal cortex in early postnatal (postnatal day 16; P16) and adult (P60) male and female mice. We found that ongoing cocaine exposure decreased BDNF expression in the E15 dorsal forebrain, prenatal cocaine exposure did not alter BDNF or TrkB (total or phosphorylated) expression in the frontal cortex at P16, and that the prenatal cocaine exposure produced significant increases in BDNF, the activated (phosphorylated) form of TrkB, as well as Bdnf mRNA in the frontal cortex at P60. The increase in BDNF protein and mRNA expression at P60 was concurrent with hyperacetylation of histone H3 at the Bdnf promoter in the frontal cortex. The increase in frontal cortical BDNF and activated TrkB at P60 occurred in male but not female mice. Thus, our data demonstrate that ongoing cocaine exposure produces a decrease in BDNF expression in the embryonic brain, and that prenatal cocaine exposure produces a sex-specific increase in frontal cortical BDNF-TrkB signaling at P60 only in male mice. Lastly, hyperacetylation of histone H3 at the Bdnf promoter is one epigenetic mechanism mediating the effects of prenatal cocaine exposure on Bdnf expression at P60 in male mice.

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“…For example, Fuchikami et al (2008) revealed decreased H3 acetylation at bdnf IV in the adult rat hippocampus after a single bout of immobilization stress (Fuchikami et al, 2009). Conversely, prenatal cocaine exposure increased H3 acetylation at bdnf IV (Kabir et al, 2014). Communal nesting in infancy and fear conditioning in adulthood have too been shown to increase bdnf IV H3 (Lubin et al, 2008, Branchi et al, 2011, Takei et al, 2011, Bredy et al, 2007) and H4 (Takei et al, 2011, Bredy et al, 2007) acetylation.…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of early-life caregiving experiences onbrain-derived neurotrophic factorhistone acetylation in the adult rat mPFC

Blaze

Asok

Roth

2015

Stress

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Infant-caregiver experiences are major contributing factors to neural and behavioral development. Research continues to indicate that epigenetic mechanisms provide a way in which infant-caregiver experiences affect gene activity and other downstream processes in the brain that influence behavioral development. Our laboratory previously demonstrated in a rodent model that exposure to maltreatment alters methylation of DNA associated with the brain derived neurotrophic factor (bdnf) and reelin genes as well as mRNA of key epigenetic regulatory genes in the medial prefrontal cortex (mPFC). In the current study we characterized patterns of histone acetylation at bdnf and reelin gene loci after our caregiver manipulations. Using a within-litter design (n=8–10/group from 8 litters), pups were exposed to adverse (maltreatment condition: exposure to a stressed caregiver) or nurturing (cross-foster condition: exposure to a nurturing caregiver) caregiving environments outside the home cage for 30 minutes each day during the first postnatal week. Remaining pups in a litter were left with the biological mother during each session (providing normal care controls). We then used chromatin immunoprecipitation (ChIP) and quantitative RT-PCR to measure histone 3 lysine 9/14 acetylation at bdnf exons I and IV and the reelin promoter in the adult mPFC. Maltreated females had decreased acetylation at bdnf IV, while neither males nor females exhibited histone acetylation alterations at bdnf I or the reelin promoter. These data demonstrate the ability of maltreatment to have long-term consequences on histone acetylation in the mPFC, and provide further evidence of the epigenetic susceptibility of bdnf IV to the quality of infant-caregiver experiences.

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Effects of Prenatal Cocaine Exposure on Social Development in Mice

Cited by 12 publications

References 48 publications

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Prenatal domoic acid exposure disrupts mouse pro-social behavior and functional connectivity MRI

Prenatal Cocaine Exposure Alters BDNF-TrkB Signaling in the Embryonic and Adult Brain

Long-term effects of early-life caregiving experiences onbrain-derived neurotrophic factorhistone acetylation in the adult rat mPFC

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