Early maternal deprivation affects dentate gyrus structure and emotional learning in adult female rats

Abstract

RationaleStress elicits functional and structural changes in the hippocampus. Early life stress is one of the major risk factors for stress-related pathologies like depression. Patients suffering from depression show a reduced hippocampal volume, and in women, this occurs more often when depression is preceded by childhood trauma. However, the underlying mechanisms that account for a reduced hippocampal volume are unknown.ObjectiveWe examined the effects of maternal absence on structure and function of the hippocampus in female offspring.MethodsWe studied whether 24 h of maternal deprivation (MD) on postnatal day 3 altered adult neurogenesis, individual neuronal morphology and dentate gyrus (DG) structure in young adult female rats. In addition, functional alterations were addressed by studying synaptic plasticity in vitro, and spatial as well as emotional learning was tested.ResultsAdult females that were subjected to MD revealed significant reductions in DG granule cell number and density. In addition, DG neurons were altered in their dendritic arrangement. No effects on the rate of adult neurogenesis were found. Furthermore, MD did not alter synaptic plasticity in vitro, neither under normal nor high-stress conditions. In addition, spatial learning and contextual fear conditioning were comparable between control and MD animals. However, MD animals showed an improved amygdala-dependent fear memory.ConclusionAlthough early life stress exposure did not impair hippocampus-dependent functioning in female offspring, it irreversibly affected DG structure by reducing cell numbers. This may be relevant for the reduced hippocampal volume observed in depression and the increased vulnerability of women to develop depression.

Effects of early-life stress on cognitive function and hippocampal structure in female rodents

“…For MD, the mother was placed in a separate cage; the pups went back in the home cage and were placed on a heating pad (32°C) in a separate room. MD litters were kept in this room for 24 h before being placed back with the dam, as described elsewhere (Oomen et al, 2011). No animals died during the MD procedure.…”

“…Adult male rats that were subjected to 24-h MD at PND 3 demonstrate reduced neurogenesis, impaired spatial memory but enhanced memory formation under stressful learning conditions . The behavioral phenotype in female rats appeared to be more subtle and confined to amygdala-dependent learning paradigms (Oomen et al, 2011). Literature on cognitive performance in adult females exposed early in life to this or other types of ELS is generally less extensive than literature on males.…”

“…More specifically, we tested: (1) general anxiety behavior in an Elevated Plus Maze (EPM, Rodgers and Dalvi, 1997); (2) reward-based decision making in a rodent version of the Iowa Gambling Task (rIGT; Van den Bos et al, 2014) (3) non-stressful contextual learning in an object recognition task (ORT, Bevins and Besheer, 2006) and an object-in-location task (OLT, adapted from Ennaceur et al, 2005). Hippocampal structural measures included dentate gyrus (DG) volume, proliferation and neurogenesis that can be altered by (early life) stress and are involved in aspects of cognition (Lucassen et al, , 2013Oomen et al, 2011Oomen et al, , 2014.…”

Early life stress and psychopharmacology

“…From the developmental perspective, Rudolph et al (2010) present a study showing how individual differences in stress sensitivity shape the clinical response to peer victimization in children. This is mirrored in the preclinical arena, with findings that animals exposed to ELS are affected in their response to drugs of abuse (Rodrigues et al 2010), cognitive function (Hedges and Woon 2010;Oomen et al 2010), anxiety-related behaviors (Peleg-Raibstein and Feldon 2010), depression-and psychosis-related behaviors (Markham and Koenig 2010), stress sensitivity and hypothalamic-pituitary-adrenal (HPA) axis function (Claessens et al 2010), and sleep (Pryce et al 2010), as well as in the brain-gut axis (modeling aspects of irritable bowel syndrome) (O'Mahony et al 2010). Certainly, limitations to these models do exist (Schmidt et al 2010;Van Waes et al 2010), reflecting a variety of individual differences (Claessens et al 2010), including whether animals are tested during adolescence or adulthood (Peleg-Raibstein and Feldon 2010).…”

“…The neuroanatomical (Oomen et al 2010;Pryce et al 2010), electrophysiological (Ali et al 2010) and neurochemical alterations following ELS that lead to these behavioral changes are increasingly well understood. O'Malley et al (2010) link alterations in central corticotrophin-releasing factor receptors to altered stress sensitivity.…”