Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans

Abstract

We studied D1 dopamine receptor (D1R) gene expression in the human striatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ([3H]SCH 23390) were detected in the striatum from week 12 of fetal life. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a pattern similar to D1R mRNA. D1R-IR was essentially present in striosomal cell bodies and neuropil, whereas only a few cell bodies were detected in the matrix. From week 20 of fetal life, D1R gene expression developed in the matrix neurons as well, thus leading to an even D1R mRNA expression throughout striosomes and matrix compartments at birth. Comparative analysis of the expression of D1R and dynorphin mRNA show the same developmental patchy pattern up to week 26. Indeed, neurons expressing the D1R gene contain dynorphin mRNA; in contrast, they do not express the preproenkephalin A gene. At birth, the pattern of D1R mRNA expression level was sharply different from that of dynorphin (DYN) gene expression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. These results demonstrate that, during human ontogeny, functional D1 receptors are expressed as early as week 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA content. Toward the end of fetal life, there is a dissociation between D1R and DYN expression levels, suggesting that neuroanatomical or neurochemical modifications occur at this period, which may contribute to the regulation of the tone of the striatal D1R and DYN gene with topological specificity.

Novel role of sorting nexin 5 in renal D 1 dopamine receptor trafficking and function: implications for hypertension

“…We next determined whether there was a similar colocalization of SNX5 and D 1 R in the caudate nucleus and putamen of the WKY rat brain. Most of the neurons in these areas express D 1 R (30). We observed discrete localization of both D 1 R and SNX5 in the neurons found at the caudate nucleus (Fig.…”

The non-human primate striatum undergoes marked prolonged remodeling during postnatal development

“…The ontogeny of the human striatum has not been studied comprehensively, and, indeed, very few studies have been done. Most studies to date have focused on the fetal brain (13–40 weeks gestation) and have shown in striatum patchy distributions with striosomal enrichments of acetylcholinesterase (AChE) and muscarinic cholinergic binding sites (Nastuk and Graybiel, 1985), AChE and NADPH-diaphorase (Sajin et al, 1992), calbindin (Letinic and Kostovic, 1996), dopamine D1 receptor and dynorphin mRNA (Brana et al, 1996), glutamate receptor scaffold kinase anchoring protein (Ulfig et al, 2001), and synaptophysin (Ulfig et al, 2000). A study of postnatal human brain revealed an inversion from an immature pattern of calbindin-enriched striosomes to a mature pattern of calbindin-enriched matrix sometime between term gestation to 18 months of life (Letinic and Kostovic, 1996).…”

Prenatal exposure to infection: a primary mechanism for abnormal dopaminergic development in schizophrenia

“…In rats, the same developmental phases occur approximately 2 days later (Altman and Bayer 1981;Voorn et al 1988). DA synthesizing neurons in the human fetal brain are also established very early in development, namely, at around 5 weeks post-conception (Pickel et al 1980;Brana et al 1996;Aubert et al 1997). Hence, the cascade of developmental events that leads to the establishment of the mesocorticolimbic and mesostriatal DA systems starts early in fetal life.…”