| Autor: |
Waage-Baudet, H., Lauder, J.M., Dehart, D.B., Kluckman, K., Hiller, S., Tint, G.S., Sulik, K.K. |
| Předmět: |
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| Zdroj: |
International Journal of Developmental Neuroscience; Dec2003, Vol. 21 Issue 8, p451, 9p |
| Abstrakt: |
The Smith–Lemli–Opitz syndrome (SLOS) is a malformation/mental retardation syndrome resulting from an inborn error in 3β-hydroxysteroid Δ7-reductase (DHCR7), the terminal enzyme required for cholesterol biosynthesis. Using a targeting strategy designed to virtually eliminate Dhcr7 activity, we have created a SLOS mouse model that exhibits commissural deficiencies, hippocampal abnormalities, and hypermorphic development of serotonin (5-HT) neurons. The latter is of particular interest with respect to current evidence that serotonin plays a significant role in autism spectrum disorders and the recent clinical observation that 50% of SLOS patients present with autistic behavior. Immunohistochemical analyses have revealed a 306% increase in the area of 5-HT immunoreactivity (5-HT IR) in the hindbrains of mutant (Dhcr7−/−) mice as compared to age-matched wild type animals. Amount of 5-HT IR was measured as total area of IR per histological section. Additionally, a regional increase as high as 15-fold was observed for the most lateral sagittal hindbrain sections. In Dhcr7−/− mice, an expansion of 5-HT IR into the ventricular zone and floor plate region was observed. In addition, the rostral and caudal raphe groups exhibited a radial expansion in Dhcr7−/− mice, with 5-HT IR cells present in locations not seen in wild type mice. This increase in 5-HT IR appears to represent an increase in total number of 5-HT neurons and fibers. These observations may help explain the behavioral phenotype seen in SLOS, and provide clues for future therapeutic interventions that utilize pharmacological modulation of the serotonergic system. [Copyright &y& Elsevier] |
| Databáze: |
Complementary Index |
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