Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage

Alessandro Bertolino, Joshua L. Roffman, Barbara K. Lipska, Peter Van Gelderen, Alan Olson, Daniel R. Weinberger

Research output: Contribution to journalArticle

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 postmortem 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.

Original languageEnglish
Pages (from-to)983-990
Number of pages8
JournalCerebral Cortex
Volume12
Issue number9
Publication statusPublished - Sep 2002

ASJC Scopus subject areas

  • Neuroscience(all)

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    Bertolino, A., Roffman, J. L., Lipska, B. K., Van Gelderen, P., Olson, A., & Weinberger, D. R. (2002). Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. Cerebral Cortex, 12(9), 983-990.