Early-life stress and neurometabolites of the hippocampus

Brain Res. 2010 Oct 28:1358:191-9. doi: 10.1016/j.brainres.2010.08.021. Epub 2010 Aug 14.

Abstract

We tested the hypothesis that early life stress would persistently compromise neuronal viability of the hippocampus of the grown nonhuman primate. Neuronal viability was assessed through ascertainment of N-acetyl aspartate (NAA)-an amino acid considered reflective of neuronal density/functional integrity-using in vivo proton magnetic resonance spectroscopic imaging (MRSI). The subjects reported herein represent a re-analysis of a sample of nineteen adult male bonnet macaques that had been reared in infancy under induced stress by maternal variable foraging demand (VFD) (N=10) or control rearing conditions (N=9). The MRSI spectral readings were recorded using a GE 1.5 Tesla machine under anesthesia. Relative NAA values were derived using NAA as numerator and both choline (Cho) or creatine (Cr) as denominators. Left medial temporal lobe (MTL) NAA/Cho but not NAA/Cr was decreased in VFD subjects versus controls. An MTL NAA/Cho ratio deficit remained significant when controlling for multiple confounding variables. Regression analyses suggested that the NAA/Choline finding was due to independently low left NAA and high left choline. Right MTL showed no rearing effects for NAA, but right NAA was positively related to body mass, irrespective of denominator. The current data indicate that decreased left MTL NAA/Cho may reflect low neuronal viability of the hippocampus following early life stress in VFD-reared versus normally-reared subjects. Given the importance of the hippocampus in stress-mediated toxicity, validation of these data using absolute quantification is suggested and correlative neurohistological studies of hippocampus are warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Choline / metabolism*
  • Creatine / metabolism
  • Functional Laterality
  • Hippocampus / metabolism*
  • Macaca mulatta
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Maternal Deprivation
  • Regression Analysis
  • Spectrum Analysis
  • Stress, Psychological / metabolism
  • Stress, Psychological / pathology*

Substances

  • Aspartic Acid
  • N-acetylaspartate
  • Creatine
  • Choline