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Journal of Neuroscience, Vol 7, 1994-2018, Copyright © 1987 by Society for Neuroscience
Development of a dopamine- and cyclic adenosine 3':5'-monophosphate- regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation
GA Foster, M Schultzberg, T Hokfelt, M Goldstein, HC Hemmings Jr, CC Ouimet, SI Walaas and P Greengard
The development of a dopamine- and adenosine 3':5'-monophosphate- regulated
phosphoprotein with an apparent Mr of 32,000 (DARPP-32) has been
investigated in the central nervous system of the prenatal and newborn rat
by immunocytochemical methods. DARPP-32 first appears in the rat brain at
day 14 of gestation, in the anlage of the primary olfactory cortex and the
caudate nucleus. Over the next few days, the number of immunoreactive cell
bodies in these 2 areas, and in the olfactory tubercle and frontal cortex,
increases rapidly. By the day of birth, most of the brain regions that will
ultimately contain DARPP-32- positive somata already display a disposition
toward DARPP-32-like immunoreactivity similar to that observed in the adult
animal. In addition to the nuclei mentioned above, DARPP-32-containing cell
bodies also appear over the intervening period in the olfactory nucleus,
nucleus accumbens, central amygdaloid nucleus, lateral funiculus, and the
choroid plexus and ependymal layers of the third, fourth, and lateral
ventricles and the Sylvian aqueduct. Many of these immunoreactive cells
disappear during subsequent postnatal maturation. DARPP-32-immunoreactive
fibers were also observed in the prenatal and newborn rat CNS. As in the
adult, the processes were observed in known target areas of the
DARPP-32-containing neurons, namely, the globus pallidus, ventral pallidum,
internal capsule, and substantia nigra. The ontogeny of tyrosine
hydroxylase (TH)-like immunoreactivity was analyzed simultaneously. Of
particular interest was the observation that the arrival within a given
brain region of the presumed dopaminergic, TH-containing innervation, part
of whose postsynaptic function is putatively mediated by DARPP-32, was
preceded by at least 2 d by the appearance of the DARPP-32-containing
cells. Moreover, the subsequent reorganization of the DARPP-32-positive
somata within the caudate nucleus into distinct clumps also predated by 1
or 2 d the aggregation of the TH fibers into the same microzones. The
development of DARPP-32-like immunoreactivity is mostly complete by the day
of birth, and is consistent with its playing a role in mediating some of
the postsynaptic actions of dopamine pathways. The appearance of this
protein does not seem to be dependent on the presence of a dopaminergic
innervation.
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