Segregation of human neural stem cells in the developing primate forebrain.

Many central nervous system regions at all stages of life contain neural stem cells (NSCs). We explored how these disparate NSC pools might emerge. A traceable clone of human NSCs was implanted intraventricularly to allow its integration into cerebral germinal zones of Old World monkey fetuses. The NSCs distributed into two subpopulations: One contributed to corticogenesis by migrating along radial glia to temporally appropriate layers of the cortical plate and differentiating into lamina-appropriate neurons or glia; the other remained undifferentiated and contributed to a secondary germinal zone (the subventricular zone) with occasional members interspersed throughout brain parenchyma. An early neurogenetic program allocates the progeny of NSCs either immediately for organogenesis or to undifferentiated pools for later use in the "postdevelopmental" brain.

Neural transplantation of hNT neurons for Huntington's disease.

Fetal striatal tissue transplants have been shown to restore motor deficits in rat and monkey models of Huntington's disease (HD). In the present study, using rats with unilateral striatal lesions, we compared fetal striatal tissue transplants to transplants of human NT (hNT) neurons. hNT neurons are terminally differentiated cells derived from the human NTera-2 cell line. In vitro, we have found that purified hNT neurons have a biochemical phenotype similar to that of human fetal striatal tissue. Both hNT neurons and fetal striatal tissue express mRNAs for glutamic acid decarboxylase, choline acetyltransferase, and the D1 and D2 dopamine receptors. Grafts of either hNT neurons or fetal striatal tissue into unilateral quinolinic acid-lesioned rat striatum improved methamphetamine-induced circling behavior. Sham controls showed no changes in methamphetamine-induced circling behavior. In the staircase test for skilled forelimb use, both transplant groups showed partial recovery in skilled use of the paw contralateral to the side of lesion, whereas the control animals showed continued deficits. These findings suggest that transplantation of hNT neurons may be an alternative to transplantation of fetal striatal tissue in the treatment of HD.

Avascular necrosis of bone in dyskeratosis congenita.

A case of dyskeratosis congenita, a rare X-linked disorder, is presented. The patient had the classic triad of cutaneous findings: reticulated hyperpigmentation, nail dystrophy, and leukoplakia. In addition, a previously unreported finding developed, avascular necrosis of bone without systemic steroid therapy. Recognition of this disorder is important because pancytopenia and malignancy develop in up to 50 percent of patients.

Heart-rate correlates of childhood activities: play, exploration, problem-solving and day-dreaming.

Heart-rate was monitored while children were engaged in different activities. The first study examined the hypothesis that the behavioural distinction between exploration and play would be supported by the psychophysiological measure. Two-year-olds showed suppression of heart rate variability (HRV) during exploration, and even more during solution of a puzzle, suggesting that the task demands these two activities were greater than those during play. The second study demonstrated a relationship between HRV during daydreaming and during problem solving in 9-year-old children which was similar to that obtained between play and problem solving in younger children. The correlative use of HRV thus strengthened functional interpretations of behaviour.

Biological bases of psychological sex differences.

The mammalian process of sexual differentiation is briefly outlined. It is argued that in becoming girl or boy there are certain constraints and biases placed on the developing individual, some of these stemming from physiological bases, others from sensory-perceptual ones. These bases in turn affect the salience environmental factors for the two sexes. The different "behavioral styles" of boys and girls are thus a consequence of the transaction between the environment and these predispositions. The psychosexual anomalies are reviewed as instructive cases. Differences in neural organization and cerebral asymmetry are considered as further evidence of sexual dimorphism in humans.

Interaction between bromocriptine and levodopa. Biochemical basis for an improved treatment for parkinsonism.

The present investigation examined the biochemical interaction of bromocriptine and levodopa with respect to monoamine and gamma-aminobutyric acid metabolism in the brain. Rats were treated with levodopa, 250 mg per kilogram of body weight intraperitoneally, with or without carbidopa, 25 mg per kilogram, 1 or 2 hours before sacrifice. Some were also given bromocriptine, 5.0 mg per kilogram, 4 hours before sacrifice. Rats were killed 1 and 2 hours after levodopa and brain levels of gamma-aminobutyric acid and monoamines, and their metabolites were measured. Dopamine levels and metabolism were not markedly altered when bromocriptine was added to levodopa treatment. The level of serotonin, which was reduced 25 to 40 percent by levodopa alone, was close to normal with the combination treatment. Serotonin metabolism was also enhanced by the addition of bromocriptine as shown by increased levels of 5-hydroxyindoleacetic acid. The results suggest that bromocriptine not only may improve the motor disorder of parkinsonism but also may reduce some side effects of levodopa therapy, such as depression, which could be due to serotonin depletion.

Correlation of behavioural inhibition or excitation produced by bromocriptine with changes in brain catecholamine turnover.

The dopamine agonist, bromocriptine, produced either inhibition or stimulation of motor behaviour in rats depending upon the dose and time after administration. Stimulation of motor activity occurred only with high doses after a 1-2 h delay. Both inhibition and stimulation were associated with decreased turnover of dopamine in the brain. Release of noradrenaline in brain and noradrenaline plus adrenaline in adrenal varied with motor activity. It is suggested that low doses of bromocriptine inhibit behaviour by activating an inhibitory presynaptic receptor, resulting in reduced synthesis and release of dopamine, whilst high doses cause behavioural excitation by activating the post-synaptic dopamine receptor.

Cardiac arrhythmia and behaviour in autistic children.

The behavior and heart rate of autistic children were simultaneously videorecorded in a standard situation. Normal children of two age-groups were also studied. It was found that the heart rate of the autists was characteristically highly variable and more so than that of normal children of the same age or younger. This variability (arrhythmia) however, was behaviour-dependent in all children-involvement in a task resulting in suppresion of the arrhythmia. It was at a maximum in the autists during the performance of stereotyped behaviours. The functional implications of these behaviour-heart rate associations are discussed.