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- Title
Reduced N-Acetylaspartate in Prefrontal Cortex of Adult Rats with Neonatal Hippocampal Damage.
- Authors
Bertolino, Alessandro; Roffman, Joshua L.; Lipska, Barbara K.; van Gelderen, Peter; Olson, Alan; Weinberger, Daniel R.
- Abstract
Previous studies in animals suggested that neonatal lesions of the ventral hippocampus disrupt development of prefrontal cortex and its regulation of dopaminergic activity. In the present study, we assayed an in vivo chemical marker of neuronal integrity (proton magnetic resonance spectroscopy signal of N-acetylaspartate, NAA) in prefrontal cortex and striatum of rats with neonatal excitotoxic lesions of the ventral hippocampus. We also measured in post-mortem tissue expression of EAAC1 mRNA, a molecular marker of intrinsic neurons. In the cohort studied at juvenile age and again at young adulthood [postnatal day (PD) 37 and 71], we found selective reductions of NAA in the prefrontal cortex only at PD 71. Emergence of neuronal pathology was temporally associated with emergence of amphetamine-induced hyperlocomotion. Reduced prefrontal NAA was confirmed in the second cohort studied at an older age (PD 120). Expression of EAAC1 mRNA was significantly reduced in prefrontal cortex of the lesioned rats. No changes in NAA were found in the striatum in either cohort and cortical area size was not changed. These results suggest that early ventral hippocampal lesions produce developmental neuronal pathology in prefrontal cortex that is temporally associated with dysregulation of dopamine behaviors and is reminiscent of the temporal profile of the onset of schizophrenia.
- Publication
Cerebral Cortex, 2002, Vol 12, Issue 9, p983
- ISSN
1047-3211
- Publication type
Article
- DOI
10.1093/cercor/12.9.983