Abstract
New neurons continue to be generated in the dentate gyrus (DG) region of the hippocampus throughout adulthood, and abnormal regulation of this process has emerged as an endophenotype common to several psychiatric disorders. Previous research shows that genetic risk factors associated with schizophrenia alter the maturation of adult-generated neurons. Here, we investigate whether early adversity, a potential environmental risk factor, similarly influences adult neurogenesis. During the first 2 weeks of postnatal life, mice were subject to repeated and unpredictable periods of separation from their mothers. When the mice reached adulthood, pharmacological and retroviral labelling techniques were used to assess the generation and maturation of new neurons. We found that adult mice that were repeatedly separated from their mothers early in life had similar rates of proliferation in the DG, but had fewer numbers of cells that survived and differentiated into neurons. Furthermore, neurons generated in adulthood had less complex dendritic arborization and fewer dendritic spines. These findings indicate that early adverse experience has a long-lasting impact on both the number and the complexity of adult-generated neurons in the hippocampus, suggesting that the abnormal regulation of adult neurogenesis associated with psychiatric disorders could arise from environmental influence alone, or from complex interactions of environmental factors with genetic predisposition.
Highlights
IntroductionWe investigate whether adverse experiences early in life can lead to changes in the regulation of hippocampal neurogenesis during adulthood
Previous studies in rodents report that early adversity, in the form of separation from the mother during the initial postnatal weeks, alters the number and morphology of developmentally generated dentate gyrus (DG) neurons.[14,15,16,17]
We show that the effects of early adversity on the generation and maturation of new DG neurons persist long after the adverse events initially take place
Summary
We investigate whether adverse experiences early in life can lead to changes in the regulation of hippocampal neurogenesis during adulthood. Adversity was modelled in mice using a chronic unpredictable maternal separation paradigm,[8,9] in which mouse pups were separated from their mothers for 3 h a day during the first 2 postnatal weeks. When these mice reached adulthood, we assessed the proliferation, survival, differentiation and morphological maturation of new neurons in the DG. Similar to some genetic manipulations, adverse early experiences have a long-lasting impact on both the number and the complexity of hippocampal neurons generated during adulthood
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