Neurotransmitters, neuropeptides and calcium binding proteins in developing human cerebellum: A review

Many endogenous neurochemicals that are known to have important functions i n the mature central nervous system have also been found in the developing human cerebellum. Cholinergic neurons, as revealed by immunoreactivities to wards choline acetyltransferase or acetylcholinesterase, appear early at 23 weeks of gestation in the cerebellar cortex and deep nuclei. Immunoreactiv ities gradually increase until the first postnatal month. Enkephalin is loc alized in the developing cerebellum, initially in the fibers of the cortex and deep nuclei at 16-20 weeks and then also in the Purkinje cells, granule cells, basket cells and Golgi cells at 23 weeks onward. Another neuropepti de, substance P, is localized mainly in the fibers of the dentate nucleus f rom 9 to 24 weeks but substance P immunoreactivity declines thereafter. GAB A, an inhibitory neurotransmitter of the central nervous system, starts to appear at 16 weeks in the Purkinje cells, stellate cells, basket cells, mos sy fibers and neurons of deep nuclei. GABA expression is gradually upregula ted toward term forming networks of GABA-positive fibers and neurons. Catec holaminergic fibers and neurons are also detected in the cortex and deep nu clei at as early as 16 weeks. Calcium binding proteins, calbindin D28K and parvalbumin, make their first appearance in the cortex and deep nuclei at 1 4 weeks and then their expression decreases toward term, while calretinin a ppears later at 21 weeks but its expression increases with fetal age. The a bove findings suggest that many neurotransmitters, neuropeptides and calciu m binding proteins (1) appear early during development of the cerebellum; ( 2) have specific temporal and spatial expression patterns; (3) may have fun ctions other than those found in the mature neural systems; and (4) may be able to interact with each other during early development.