Biology subjects

van IJzendoorn, M. H.

Publications and source records attributed to van IJzendoorn, M. H..

3 recordsLinked to original sources

bioRxiv2020

Effects of maternal deprivation and complex housing on pro-social behavior in rats: An automated, operant task examining motivation to liberate a trapped conspecific

Early life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. Here, we aimed to study how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we adapted an existing paw operated liberation task to an automated operant task, to measure motivation (by progressively increasing required lever pressing) to liberate a trapped conspecific. Liberation of the trapped rat resulted either in social contact, or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectation, the trapped configuration resulted in a reduced motivation to act. Early postnatal stress (24h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while motivation for a sucrose reward was not affected.

animal behavior and cognition↗

bioRxiv2020

Epigenome-wide change and variation in DNA methylation from birth to late adolescence

DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.

genomics↗

bioRxiv2019

Maternal care of heterozygous Dopamine Receptor D4 knockout mice: Differential susceptibility to early-life rearing conditions

The differential susceptibility hypothesis proposes that individuals who are more susceptible to the negative effects of adverse rearing conditions may also benefit more from enriched environments. Evidence derived from human experiments suggests the lower efficacy dopamine receptor D4 (DRD4) 7-repeat as a main factor in exhibiting these for better and for worse characteristics. However, human studies lack the genetic and environmental control offered by animal experiments, complicating assessment of causal relations. To study differential susceptibility in an animal model, we exposed Drd4+/- mice and control litter mates to a limited nesting/bedding (LN), standard nesting (SN) or communal nesting (CN) rearing environment from postnatal day (P) 2-14. Puberty onset was examined from P24-P36 and adult females were assessed on maternal care towards their own offspring. In both males and females, LN reared mice showed a delay in puberty onset that was partly mediated by a reduction in body weight at weaning, irrespective of Drd4 genotype. During adulthood, LN reared females exhibited characteristics of poor maternal care, whereas dams reared in CN environments showed lower rates of unpredictability towards their own offspring. Differential susceptibility was observed only for licking/grooming levels of female offspring towards their litter; LN reared Drd4+/- mice exhibited the lowest and CN reared Drd4+/- mice the highest levels of licking/grooming. These results indicate that both genetic and early-environmental factors play an important role in shaping maternal care of the offspring for better and for worse.

developmental biology↗