The function of N-acetyl-L-aspartate (NAA), a predominant substance in the CNS, has not yet been determined. To investigate the possible function of NAA as a lipid precursor [¹⁴C]-N-acetyl-L-aspartate (NAA) or [¹⁴C]-acetate (AcA) was injected intracerebrally into 8, 15- and 22-day-old rats. These time points were selected because NAA concentration and the activity of the NAA synthetizing enzyme L-aspartate-N-acetyltransferase (ANAT) were low in 8-day-old rats, intermediate in 15-day-old rats and high in 22-day-old rats. During an incubation period of 4 h the radioactive acetyl group of NAA is incorporated into the lipid fraction in amounts of 42.9 to 65.7% of recovered total radioactivity, increasing with the age of the rats. In contrast, radioactivity incorporated from AcA is constant for all three ages. With NAA as precursor only 7.2–9.4% of the recovered total radioactivity is incorporated into the protein fraction. With AcA as precursor 27.0–18.1% of recovered radioactivity is incorporated into the protein fraction, the amounts decreasing with age. Taking into account that in vivo NAA concentration in the brain is much higher than the AcA concentration, NAA is clearly the more efficient precursor for lipid synthesis than AcA. Further, we compared NAA and AcA as lipid precursors by analyzing the radioactivity in single lipid fractions, expressed as normalized specific incorporation or normalized incorporation. The measured differences between NAA and AcA in normalized specific and normalized incorporation of acetyl groups imply that NAA is not simply degraded to AcA before incorporated into lipids. We conclude that NAA is a major source of acetyl groups for lipid synthesis during rat brain development.

This review summarizes the temporal relations between selected psychological milestones in the first year of the human infant and theoretically relevant developmental neurobiological changes in the brain, supplemented where appropriate, with evidence from the non-human primate. The disappearance of the palmar grasp reflex and the decrease in endogenous smiling and spontaneous crying, which occur at 2-3 months, are correlated to emergent cortical inhibition of brainstem circuits. In addition, the improved ability to recognize an event experienced in the immediate past (recognition memory) is related to growth of the hippocampus and adjacent structures at this age. The behavioral developments at 7-10 months include an enhanced ability to retrieve stored representations of the past and to compare past and present (working memory), along with the emergence of the universal fears of strangers and separation from the caretaker. These milestones are correlated in time with maturational changes in the prefrontal and rhinal cortices and hippocampal formation, the integration of the limbic system and increased responsiveness of the hypothalamus-pituitary-adrenal axis. Knowledge of age-dependent correlations of brain and behavioral maturation is a basis for the investigation of causal relationships between brain development and behavior. A close collaboration of pediatricians, psychologists and neuroscientists is, therefore, necessary.

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied by in vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1HMR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infant's behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants. Eighteen preterm infants unremarkable with respect to neurologic and medical status were studied at approximately 2 wk of postnatal age [gestational age (GA) 1: 32.5 +/- 1.2 wk] and again at term (GA 2: 40.0 +/- 1.1 wk). For comparison a group of 13 full-term born infants (GA T: 40.6 +/- 2.1 wk) were studied by MR and six by APIB. When GA 2 to GA 1 was compared, significant maturational changes were found with MRI in gray and white matter and myelination, with 1H MRS in the concentration of N-acetylaspartate and with all scores of APIB. In preterm infants at term (GA 2) compared with full-term infants (GA T) significantly less gray and white matter differentiation and myelination was observed as well as significantly poorer performance in four neurobehavioral parameters (autonomic reactivity, motoric reactivity, state organization, attentional availability). We conclude that MRI and 1H MRS can be used to study postnatal brain development in preterm infants. Structural and biochemical maturation is accompanied by functional maturation as shown with the neurobehavior assessment. Preterm infants at term compared with full-term infants show a structural as well as a functional delay in brain development assessed at 40 wk of postconceptional age.

In structural brain development eight interrelated but distinguishable events can be recognized: (1) neuronal induction, (2) neuroblast proliferation, (3) neuronal migration, (4) neuronal selective aggregation, (5) neuronal differentiation and formation of specific patterns of connection, (6) neuronal death, (7) selective synapse elimination and (8) myelination. The basic mechanisms regulating these developmental events are genetically determined but at any stage of development epigenetic and environmental factors modulate the genetic regulation. This paper reviews representative samples of work in animal experiments and knowledge in human fetal brain development by several authors.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol. The age-dependent changes of in vivo molar concentrations of N-acetylaspartate, choline, taurine, and inositol were estimated in preterm babies, babies at term, and adults. The range of postconceptional age in the studied babies was 31 to 45 wk. Taking the biochemically measured creatine concentrations in age-corresponding autopsy material as an internal standard, the in vivo concentrations of the other metabolites were calculated from the proton spectra. N-acetylaspartate showed an increase from 1.9 mM in preterm babies to 3.1 mM in term babies and to 6.5 mM in adult brain. Taurine was noted to increase from 1.1 mM in preterm infants to 2.3 mM in term infants and did not decrease significantly in adult brain. Choline and inositol concentrations did not change significantly throughout the studied age groups. These new data on in vivo, localized 1H-spectroscopy show that it is a sensitive method for studying early metabolic brain development in humans.