In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Lakshmi Raman, Ivan Tkac, Kathleen Ennis, Michael K. Georgieff, Rolf Gruetter, Raghavendra Rao

Research output: Contribution to journalArticle

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Abstract

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 μl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myo-inositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P < 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalDevelopmental Brain Research
Volume156
Issue number2
DOIs
StatePublished - May 12 2005

Fingerprint

Hippocampus
Glutamic Acid
Phosphocreatine
Creatine
Glutamine
Synaptic Transmission
gamma-Aminobutyric Acid
Neurochemistry
Brain
Inositol
Hypoxia
Aspartic Acid
Energy Metabolism
Glutathione
Heart Diseases
Phospholipids
Magnetic Resonance Spectroscopy
Wounds and Injuries

Keywords

  • H NMR spectroscopy
  • Chronic hypoxia
  • Hippocampus
  • Phosphocreatine
  • Rat

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus. / Raman, Lakshmi; Tkac, Ivan; Ennis, Kathleen; Georgieff, Michael K.; Gruetter, Rolf; Rao, Raghavendra.

In: Developmental Brain Research, Vol. 156, No. 2, 12.05.2005, p. 202-209.

Research output: Contribution to journalArticle

Raman, Lakshmi ; Tkac, Ivan ; Ennis, Kathleen ; Georgieff, Michael K. ; Gruetter, Rolf ; Rao, Raghavendra. / In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus. In: Developmental Brain Research. 2005 ; Vol. 156, No. 2. pp. 202-209.
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