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 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 (US)
Pages (from-to)983-990
Number of pages8
JournalCerebral Cortex
Volume12
Issue number9
StatePublished - Sep 2002
Externally publishedYes

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Prefrontal Cortex
Hippocampus
Pathology
Newborn Animals
Messenger RNA
Amphetamine
Dopamine
Schizophrenia
N-acetylaspartate
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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

Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. / Bertolino, Alessandro; Roffman, Joshua L.; Lipska, Barbara K.; Van Gelderen, Peter; Olson, Alan; Weinberger, Daniel.

In: Cerebral Cortex, Vol. 12, No. 9, 09.2002, p. 983-990.

Research output: Contribution to journalArticle

Bertolino, A, Roffman, JL, Lipska, BK, Van Gelderen, P, Olson, A & Weinberger, D 2002, 'Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage', Cerebral Cortex, vol. 12, no. 9, pp. 983-990.
Bertolino A, Roffman JL, Lipska BK, Van Gelderen P, Olson A, Weinberger D. Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. Cerebral Cortex. 2002 Sep;12(9):983-990.
Bertolino, Alessandro ; Roffman, Joshua L. ; Lipska, Barbara K. ; Van Gelderen, Peter ; Olson, Alan ; Weinberger, Daniel. / Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. In: Cerebral Cortex. 2002 ; Vol. 12, No. 9. pp. 983-990.
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