Developmental characteristics of neuronal nitric oxide synthase (nNOS) immunoreactive neurons in fetal to adolescent human brains.

The developmental characteristics of the neuronal nitric oxide synthase (nNOS) immunoreactive neurons in the human brain were studied. In the frontal lobe, nNOS immunoreactive cells appeared as early as 18 gestational weeks (GW) in the subcortical plate and then increased predominantly in the subcortical white matter during the fetal period, while weakly immunoreactive neurons were found in the cortical II-IV layers after 26 GW. In the basal ganglia, immunoreactive neurons could be detected in the striatum as early as 13 GW, and then showed a transient increase with peaks at 23-24 GW and 33-36 GW in the putamen and caudate nucleus, respectively. In the cerebellum, immunoreactivity was detected in the Purkinje and basket cells after 23 GW and 31 GW, respectively. The immunoreactivity of internal granule cells was constantly weak. In the brain stem, constant and intense immunoreactive neurons were found in the central gray, pedunculopontine tegmental nucleus, solitary tract nucleus, and lateral reticular nucleus. The immunoreactivity in the neurons of the pontine nucleus and inferior olivary nucleus was transiently increased, with peaks at 38-40 GW and 23-24 GW, respectively. This characteristic nNOS development suggests that transient nNOS hyperproduction may contribute to neuron maturation as well as vulnerability in each period and region, and NO may play an important role in the basic development of human brain functions.