Early emergence of altered 5‐HT 2A receptor‐evoked behavior, neural activation and gene expression following maternal separation

2017 ◽  
Vol 65 (1) ◽  
pp. 21-28 ◽  
Author(s):  
Ankit Sood ◽  
Sthitapranjya Pati ◽  
Amrita Bhattacharya ◽  
Karina Chaudhari ◽  
Vidita A. Vaidya
2012 ◽  
Vol 27 (3) ◽  
pp. 393-397 ◽  
Author(s):  
J. J. Dimatelis ◽  
N. S. Pillay ◽  
A. K. Mutyaba ◽  
V. A. Russell ◽  
W. M. U. Daniels ◽  
...  

2021 ◽  
Vol 5 ◽  
pp. 247054702110671
Author(s):  
Erika Kestering-Ferreira ◽  
Saulo Gantes Tractenberg ◽  
Francisco Sindermann Lumertz ◽  
Rodrigo Orso ◽  
Kerstin Camile Creutzberg ◽  
...  

Introduction: Disruption of maternal care using maternal separation (MS) models has provided significant evidence of the deleterious long-term effects of early life stress. Several preclinical studies investigating MS showed multiple behavioral and biomolecular alterations. However, there is still conflicting results from MS studies, which represents a challenge for reliability and replicability of those findings. Objective: To address that, this study was conducted to investigate whether MS would affect anxiety-like behaviors using a battery of classical tasks, as well as central and peripheral stress-related biomarkers. Methods: Male Balb/c mice were exposed to MS from postnatal day (PND) 2 to 14 for 180-min per day. Two independent cohorts were performed to evaluate both baseline and anxiety-like behavior responses to MS at PND60. We performed composite scores to evaluate MS effects on anxiety and risk assessment phenotypes. Also, we assessed mRNA gene expression in the medial pre-frontal cortex (mPFC) of glucocorticoid and mineralocorticoid receptors (GR and MR) using real-time PCR and peripheral corticosterone levels (CORT) to investigate possible neurobiological correlates to anxiety behaviors. Results: We found increased anxiety-like behavior and decreased risk assessment and exploratory behaviors in MS mice. The animals exposed to MS also presented a decrease in MR mRNA expression and higher levels of CORT compared to controls. Conclusions: Our findings reinforce the body of evidence suggesting that long-term MS induces effects on anxiety and risk assessment phenotypes following the exposure to a standardized MS protocol. Moreover, MS affected the expression of MR mRNA and induced significant changes on CORT response. This data highlights that the reprograming MS effects on HPA axis could be mediate by MR gene expression in mPFC and chronic overactivity of peripheral CORT levels.


2002 ◽  
Vol 3 (3) ◽  
pp. 119-131 ◽  
Author(s):  
Maureen W. Groër ◽  
Janet Hill ◽  
J. Erby Wilkinson ◽  
Alice Stuart

The purpose of this pilot study was to investigate selected stress, immune, and growth consequences of maternal separation and separation with supplemental stroking in neonatal BALB/c infant mice and their dams. Three groups of 5 litters each (7 pups per litter) were studied. Control litters were undisturbed. Separated litters experienced 3 h of daily maternal deprivation on postnatal days 6 to 10. Separated/stroked litters were separated also, but for 2 h, which was then followed by 1 h of stroking with a wet paintbrush to simulate maternal tactile stimulation. After the experimental period, all animals were returned to the nest and left undisturbed for 5 additional days. One pup fromeac h litter was sacrificed on postnatal days 6, 8, 10, and 15. Spleens and thymuses were removed, weighed, and homogenized for cell sorting, cytokine analysis, and proliferation studies. Blood was drawn for corticosterone levels and hematocrit. Hematocrits and thymus weights were lower in separated mice, suggesting decreased growth and protein synthesis. Separated/stroked pups had increased splenic proliferation responses to conconavalin A and phytohemagglutinin at day 15. Separated dams’ proliferative response to Con A was lower than control dams at day 15. Day 15 decreases in thymic CD8 cells occurred in pups, with an increased thymic H:S ratio in separated pups. CD90 cells were higher at day 15 in separated/stroked pups as were CD25s at day 10 in spleen and thymus. However, gene expression of cytokines was not measurable in spleen and thymic cells, with the exception of-IFN in separated/stroked animals. Pooled organ homogenates were used in this preliminary work, and further studies are needed to more precisely analyze the stress, immune, and growth effects of these interventions.


2021 ◽  
Vol 11 (3) ◽  
pp. 209
Author(s):  
Lene Lundgaard Donovan ◽  
Kim Henningsen ◽  
Anne Flou Kristensen ◽  
Ove Wiborg ◽  
John Dirk Nieland ◽  
...  

Depression is one of the most prevalent mental diseases worldwide. Patients with psychiatric diseases often have a history of childhood neglect, indicating that early-life experiences predispose to psychiatric diseases in adulthood. Two strong models were used in the present study: the maternal separation/early deprivation model (MS) and the chronic mild stress model (CMS). In both models, we found changes in the expression of a number of genes such as Creb and Npy. Strikingly, there was a clear regulation of expression of four genes involved in the AP-1 complex: c-Fos, c-Jun, FosB, and Jun-B. Interestingly, different expression levels were observed depending on the model, whereas the combination of the models resulted in a normal level of gene expression. The effects of MS and CMS on gene expression were associated with distinct histone methylation/acetylation patterns of all four genes. The epigenetic changes, like gene expression, were also dependent on the specific stressor or their combination. The obtained results suggest that single life events leave a mark on gene expression and the epigenetic signature of gene promoters, but a combination of different stressors at different life stages can further change gene expression through epigenetic factors, possibly causing the long-lasting adverse effects of stress.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Lauren Allen McKibben ◽  
Yogesh Dwivedi

Abstract Background The hypothalamus plays a key role in the stress response. While early life stress (ELS) increases susceptibility to psychiatric disorders including major depressive disorder (MDD), acute stress during adulthood can also precipitate MDD after ELS. Aim Here, we tested the expression of miRNAs following ELS and susceptibility to depression-like behavior and whether sex or acute stress exacerbates this response. We also tested whether environmental enrichment (Enr) promotes early life and adult behavioral stress resilience and its effect on hypothalamic miRNA and gene expression. Following rat maternal separation (MS) as an ELS model, Enr from weaning through adulthood, and restraint (RS) as acute adult stress, we tested both animal behavior and miRNA expression in the hypothalamus. Target genes and their enrichment and ontology were analyzed using bioinformatic tools. Target gene expression changes were tested using qPCR, and miRNA promoter methylation was studied using methylated-DNA immunoprecipitation qPCR. Results MS, Enr, RS, and sex altered hypothalamic miRNAs, including several previously reported in MS literature: miRs-29, − 124, − 132, − 144, − 504. Sex had a significant effect on the greatest number of miRNAs. Also, Enr reversed downregulation of miR-29b-1-5p and -301b-3p in MS. qPCR showed that MAPK6 and MMP19, targets of miR-301b-3p, were upregulated in MS and reversed by Enr. Additionally, miR-219a was hypermethylated in MS coinciding with decreased miR-219a expression. Conclusions This study found that sex plays a critical role in the hypothalamic miRNA response to both ELS and acute stress, with males expressing greater changes following postnatal stress. Moreover, enrichment significantly altered behavior as well as hypothalamic miRNA expression and their gene targets. Because of its role as the initiator of the autonomic stress response and connection to hedonic and motivational behavior, the hypothalamic miRNA landscape may significantly alter both the short and long-term behavioral response to stress.


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