Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression analysis, were evaluated in hippocampal pyramidal neurons excised by laser capture microdissection. Following maternal cocaine exposure, global DNA methylation was significantly decreased at P3 and increased at P30. Among the 492 CGIs whose methylation was significantly altered by cocaine at P3, 34% were hypermethylated while 66% were hypomethylated. Several of these CGIs contained promoter regions for genes implicated in crucial cellular functions. Endogenous expression of selected genes linked to the abnormally methylated CGIs was correspondingly decreased or increased by as much as 4–19-fold. By P30, some of the cocaine-associated effects at P3 endured, reversed to opposite directions, or disappeared. Further, additional sets of abnormally methylated targets emerged at P30 that were not observed at P3. Taken together, these observations indicate that maternal cocaine exposure during the second and third trimesters of gestation could produce potentially profound structural and functional modifications in the epigenomic programs of neonatal and prepubertal mice.

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Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.

The auditory magnetic event-related fields (ERF) qualitatively change through the child development, reflecting maturation of auditory cortical areas. Clicks presented with long inter-stimulus interval produce distinct ERF components, and may appear useful to characterize immature EFR morphology in children. The present study is aimed to investigate morphology of the auditory ERFs in school-age children, as well as lateralization and repetition suppression of ERF components evoked by the clicks. School-age children and adults passively listened to pairs of click presented to the right ear, left ear or binaurally, with 8-11 s intervals between the pairs and a 1 s interval within a pair. Adults demonstrated a typical P50m/N100m response. Unlike adults, children had two distinct components preceding the N100m-P50m (at ~65 ms) and P100m (at ~100 ms). The P100m dominated the child ERF, and was most prominent in response to binaural stimulation. The N100m in children was less developed than in adults and partly overlapped in time with the P100m, especially in response to monaural clicks. Strong repetition suppression was observed for P50m both in children and adults, P100m in children and N100m in adults. Both children and adults demonstrated ERF amplitude and/or latency right hemispheric advantage effects that may reflect right hemisphere dominance for preattentive arousal processes. Our results contribute to the knowledge concerning development of auditory processing and its lateralization in children and have implications for investigation of the auditory evoked fields in developmental disorders.