BackgroundChildren whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood.ResultsMice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks.ConclusionsUsing a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

It is possible to assess neonatal procedural pain using computer software that has good sensitivity and specificity to detect facial movements.

Preterm infants undergo several painful procedures during their stay in neonatal intensive care units. Previous studies suggest that early painful experiences may have an impact on brain development. Here, we used an animal model to investigate the effect of neonatal pain on the generation of new neurons in the dentate gyrus region of the hippocampus. Rat pups received intraplantar injections of complete Freund's adjuvant (CFA), a painful inflammatory agent, on either P1 or P8 and were sacrificed on P22. We found that rat pups injected with CFA on P8 had more BrdU-labeled cells and a higher density of cells expressing doublecortin (DCX) in the subgranular zone of the dentate gyrus. No change in BrdU-labeling or DCX expression was observed in pups injected with CFA on P1. These findings indicate that neonatal pain can increase hippocampal neurogenesis, suggesting that early painful experiences may shape brain development and thereby influence behavioral outcome.

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.

The evaluation of fetal lung maturity through GSH was more effective than the subjective method in predicting respiratory distress among newborns.