Dataset Information

Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter.

ABSTRACT: Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro.Rat pups were separated from their dams for 3 hours daily from postnatal day (PND) 2 to PND 14 or were never separated from the dam (as control animals). We isolated adult neural precursor cells from the hippocampal dentate gyrus at PND 56 and assessed rates of proliferation, apoptosis, and differentiation in cell culture. We also evaluated the effect of DNA methylation at the retinoic acid receptor (RAR) promoter stemming from NMS on adult neural precursor cells.NMS attenuated neural differentiation of adult neural precursor cells but had no detectible effect on proliferation, apoptosis, or astroglial differentiation. The DNA methyltransferase (DNMT) inhibitor, 5-aza-dC, reversed a reduction by NMS of neural differentiation of adult neural precursor cells. NMS increased DNMT1 expression and decreased expression of RAR?. An RAR? agonist increased neural differentiation and an antagonist reduced retinoic acid-induced neural differentiation. NMS increased the methylated portion of RAR? promoter, and the DNMT inhibitor reversed a reduction by NMS of RAR? messenger RNA expression.NMS attenuates the capacity of adult hippocampal neural precursor cells to differentiate into neurons by decreasing expression of RAR? through DNMT1-mediated methylation of its promoter.

SUBMITTER: Boku S

PROVIDER: S-EPMC5241093 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter.

Boku Shuken S Toda Hiroyuki H Nakagawa Shin S Kato Akiko A Inoue Takeshi T Koyama Tsukasa T Hiroi Noboru N Kusumi Ichiro I

Biological psychiatry 20140715 4

<h4>Background</h4>Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro.<h4>Methods</h ...[more]

PMID: 25127741

Similar Datasets

Project description:Early-life antibiotic exposure is associated with diverse long-term adverse health outcomes. Despite the immunomodulatory effects of gastrointestinal fungi, the impact of antibiotics on the fungal community (mycobiome) has received little attention. The objectives of this study were to determine the impact of commonly prescribed infant antibiotic treatments on the microbial loads and structures of bacterial and fungal communities in the gastrointestinal tract. Thirty-two piglets were divided into four treatment groups: amoxicillin (A), amoxicillin-clavulanic acid (AC), gentamicin-ampicillin (GA), and flavored placebo (P). Antibiotics were administered orally starting on postnatal day (PND) 1 until PND 8, except for GA, which was given on PNDs 5 and 6 intramuscularly. Fecal swabs were collected from piglets on PNDs 3 and 8, and sow feces were collected 1 day after farrowing. The impacts of antibiotics on bacterial and fungal communities were assessed by sequencing the 16S rRNA and the internal transcribed spacer 2 (ITS2) rRNA genes, respectively, and quantitative PCR was performed to determine total bacterial and fungal loads. Antibiotics did not alter the α-diversity (P = 0.834) or β-diversity (P = 0.565) of fungal communities on PND 8. AC increased the ratio of total fungal/total bacterial loads on PND 8 (P = 0.027). There was strong clustering of piglets by litter on PND 8 (P < 0.001), which corresponded to significant differences in the sow mycobiome, especially the presence of Kazachstania slooffiae. In summary, we observed a strong litter effect and showed that the maternal mycobiome is essential for shaping the piglet mycobiome in early life. IMPORTANCE This work provides evidence that although the fungal community composition is not altered by antibiotics, the overall fungal load increases with the administration of amoxicillin-clavulanic acid. Additionally, we show that the maternal fungal community is important in establishing the fungal community in piglets.

Project description:Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty.

Dataset Information

Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter.

Publications

Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets