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DARPP-32 development in the caudate nucleus is independent of afferent input from the substantia nigra
M E Ehrlich1, N L Rosen, T Kurihara
1Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Abstract:
DARPP-32, a dopamine- and adenosine 3':5'-monophosphate regulated neuronal phosphoprotein, Mr 32 kDa, is a phenotypic marker of the medium-size spiny neurons of the mammalian caudate-putamen. In the present study, we examined the ontogeny of DARPP-32 protein and mRNA, and compared it to the ontogeny of tyrosine hydroxylase and synapsin I, a synaptic-vesicle phosphoprotein. In vivo, the amount of DARPP-32 protein per mg total protein increased throughout the first three postnatal weeks, and then declined to plateau at adult levels. The mRNA level closely paralleled the protein, except that its rise preceded that of the protein. Tyrosine hydroxylase levels rose throughout the first 4 postnatal weeks, and synapsin I levels rose steadily during the same period. Primary reaggregate cultures containing cells from the caudate-putamen expressed DARPP-32 with a time course similar to that seen in vivo. The level of expression was not altered by coculturing with dopaminergic neurons from the rostral mesencephalic tegmentum. Thus, the postnatal increase in DARPP-32 levels in the caudate-putamen appears to be independent of transsynaptic or end-organ influences from the substantia nigra.
Insights
DARPP-32, a key neuronal phosphoprotein, shows developmental changes in the brain
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- DARPP-32 is a phosphoprotein and phenotypic marker for medium-size spiny neurons in the mammalian caudate-putamen.
- Its developmental regulation is crucial for understanding neuronal maturation and function.
Purpose of the Study:
- To investigate the developmental trajectory of DARPP-32 protein and mRNA in the postnatal caudate-putamen.
- To compare DARPP-32 ontogeny with tyrosine hydroxylase and synapsin I.
- To determine the influence of dopaminergic input on DARPP-32 expression.
Main Methods:
- In vivo studies of protein and mRNA levels during postnatal development.
- Analysis of DARPP-32 expression in primary reaggregate cultures of caudate-putamen neurons.
- Coculturing with dopaminergic neurons to assess transsynaptic influences.
Main Results:
- DARPP-32 protein levels increased during the first three postnatal weeks, followed by a decline to adult levels.
- DARPP-32 mRNA levels paralleled protein changes, with mRNA rise preceding protein increase.
- Tyrosine hydroxylase and synapsin I levels also increased postnatally.
- In vitro DARPP-32 expression mimicked in vivo patterns and was unaffected by dopaminergic neuron coculture.
Conclusions:
- Postnatal DARPP-32 increase in the caudate-putamen is an intrinsic developmental process.
- Expression is independent of transsynaptic or end-organ influences from the substantia nigra.