Abstract
Dopamine receptor expression in human fetal forebrain (between 6 and 20 weeks of gestation) was measured using tissue-slice receptor autoradiography with the D1-like and D2-like antagonists [3H]-SCH23390 and [3H]-YM09151- 2, respectively. Tissue sections were assayed in saturation studies and examined for age- and sex-related changes in B(max). We made the following observations: (1) the ages at which D1- and D2-like receptors were first expressed in whole forebrain sections could be reliably identified but were not significantly different from one another (gestational age 65 days for D1- vs. 72 days for D2-like receptors); (2) age-related increases in both D1- and D2-like receptors were demonstrated in forebrain and, from the middle of the first to the middle of the second trimester, the B(max) for each ligand increased by an order of magnitude after the onset of the specific binding site's expression; (3) age-related increases in D1-like receptors, but not D2-like receptors, could be demonstrated in cortex; and, (4) in one case of trisomy 18, the B(max) for [3H]-SCH23390 was significantly elevated above the 95% confidence interval when compared to an age-regressed normal sample. Although D2-like receptor density significantly increased with age in forebrain, age-regressed changes in D2-like receptor expression in cortex and striatum did not reach statistical significance. Likewise, a comparison of the mean B(max)'s by sex for both ligands in midgestational striatum failed to reach significance. These data corroborate the findings of other investigators who have delineated the ontogeny of dopaminergic systems in other animal species. The regional differences in the expression of dopamine receptor families may be relevant to the role which dopamine may play during normal gestational brain development. Moreover, significant deviations in dopamine receptor expression during gestation (as seen in this one case of trisomy 18) may signify underlying pathological processes that ultimately are manifested by abnormal psychological development and/or cognitive functioning.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 109-117 |
| Number of pages | 9 |
| Journal | Developmental Brain Research |
| Volume | 106 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Mar 12 1998 |
| Externally published | Yes |
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Keywords
- Cortex
- Dopamine or dopaminergic
- Fetal brain development or ontogeny
- Forebrain
- Neuronal differentiation
- Neurotransmitter receptor
- Striatum
ASJC Scopus subject areas
- Developmental Biology
- Developmental Neuroscience
Cite this
Ontogeny of human brain dopamine receptors I. Differential expression of [3H]-SCH23390 and [3H]-YM09151-2 specific binding. / Unis, Alan S.; Roberson, Michael D.; Robinette, Renee; Ha, James; Dorsa, Daniel.
In: Developmental Brain Research, Vol. 106, No. 1-2, 12.03.1998, p. 109-117.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ontogeny of human brain dopamine receptors I. Differential expression of [3H]-SCH23390 and [3H]-YM09151-2 specific binding
AU - Unis, Alan S.
AU - Roberson, Michael D.
AU - Robinette, Renee
AU - Ha, James
AU - Dorsa, Daniel
PY - 1998/3/12
Y1 - 1998/3/12
N2 - Dopamine receptor expression in human fetal forebrain (between 6 and 20 weeks of gestation) was measured using tissue-slice receptor autoradiography with the D1-like and D2-like antagonists [3H]-SCH23390 and [3H]-YM09151- 2, respectively. Tissue sections were assayed in saturation studies and examined for age- and sex-related changes in B(max). We made the following observations: (1) the ages at which D1- and D2-like receptors were first expressed in whole forebrain sections could be reliably identified but were not significantly different from one another (gestational age 65 days for D1- vs. 72 days for D2-like receptors); (2) age-related increases in both D1- and D2-like receptors were demonstrated in forebrain and, from the middle of the first to the middle of the second trimester, the B(max) for each ligand increased by an order of magnitude after the onset of the specific binding site's expression; (3) age-related increases in D1-like receptors, but not D2-like receptors, could be demonstrated in cortex; and, (4) in one case of trisomy 18, the B(max) for [3H]-SCH23390 was significantly elevated above the 95% confidence interval when compared to an age-regressed normal sample. Although D2-like receptor density significantly increased with age in forebrain, age-regressed changes in D2-like receptor expression in cortex and striatum did not reach statistical significance. Likewise, a comparison of the mean B(max)'s by sex for both ligands in midgestational striatum failed to reach significance. These data corroborate the findings of other investigators who have delineated the ontogeny of dopaminergic systems in other animal species. The regional differences in the expression of dopamine receptor families may be relevant to the role which dopamine may play during normal gestational brain development. Moreover, significant deviations in dopamine receptor expression during gestation (as seen in this one case of trisomy 18) may signify underlying pathological processes that ultimately are manifested by abnormal psychological development and/or cognitive functioning.
AB - Dopamine receptor expression in human fetal forebrain (between 6 and 20 weeks of gestation) was measured using tissue-slice receptor autoradiography with the D1-like and D2-like antagonists [3H]-SCH23390 and [3H]-YM09151- 2, respectively. Tissue sections were assayed in saturation studies and examined for age- and sex-related changes in B(max). We made the following observations: (1) the ages at which D1- and D2-like receptors were first expressed in whole forebrain sections could be reliably identified but were not significantly different from one another (gestational age 65 days for D1- vs. 72 days for D2-like receptors); (2) age-related increases in both D1- and D2-like receptors were demonstrated in forebrain and, from the middle of the first to the middle of the second trimester, the B(max) for each ligand increased by an order of magnitude after the onset of the specific binding site's expression; (3) age-related increases in D1-like receptors, but not D2-like receptors, could be demonstrated in cortex; and, (4) in one case of trisomy 18, the B(max) for [3H]-SCH23390 was significantly elevated above the 95% confidence interval when compared to an age-regressed normal sample. Although D2-like receptor density significantly increased with age in forebrain, age-regressed changes in D2-like receptor expression in cortex and striatum did not reach statistical significance. Likewise, a comparison of the mean B(max)'s by sex for both ligands in midgestational striatum failed to reach significance. These data corroborate the findings of other investigators who have delineated the ontogeny of dopaminergic systems in other animal species. The regional differences in the expression of dopamine receptor families may be relevant to the role which dopamine may play during normal gestational brain development. Moreover, significant deviations in dopamine receptor expression during gestation (as seen in this one case of trisomy 18) may signify underlying pathological processes that ultimately are manifested by abnormal psychological development and/or cognitive functioning.
KW - Cortex
KW - Dopamine or dopaminergic
KW - Fetal brain development or ontogeny
KW - Forebrain
KW - Neuronal differentiation
KW - Neurotransmitter receptor
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0031981257&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031981257&partnerID=8YFLogxK
U2 - 10.1016/S0165-3806(97)00202-2
DO - 10.1016/S0165-3806(97)00202-2
M3 - Article
VL - 106
SP - 109
EP - 117
JO - Developmental Brain Research
JF - Developmental Brain Research
SN - 0165-3806
IS - 1-2
ER -