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Published on: January 7, 2018
Developmental changes of (3)H-labelled mu-opioid receptors in brainstems of intra-uterine growth-restricted rats
1Laboratory of Fetal-Maternal Pathophysiology, Faculty of Sciences, University of Rouen, 76821 Mont-Saint-Aignan, France.
Insights
Intra-uterine growth restriction (IUGR) in rats leads to higher mu-opioid binding site density in the brainstem, potentially explaining increased respiratory issues in affected infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- The opioid mu-system plays a crucial role in respiratory control within the brainstem.
- Infants experiencing intra-uterine growth restriction (IUGR) exhibit a higher prevalence of respiratory disorders postnatally.
Purpose of the Study:
- To investigate the developmental changes and distribution of mu-opioid binding sites in the brainstem of rats with IUGR compared to controls.
- To explore the potential link between altered mu-opioid receptor expression and respiratory problems in IUGR.
Main Methods:
- Utilized [(3)H]DAGO, a mu-selective ligand, for autoradiography.
- Employed computer-based image analysis to quantify mu-opioid binding site density and distribution.
- Examined brainstems from embryonic day 21 (E21) through postnatal day 21 (P21) in both IUGR and control rat groups.
Main Results:
- Mu-opioid binding site density followed a similar developmental pattern in both IUGR and control rats, increasing at birth and stabilizing postnatally.
- Binding sites were heterogeneously distributed, with higher concentrations in dorsal medulla and pons, particularly in cardio-respiratory nuclei.
- IUGR rats exhibited significantly higher DAGO-binding density across most ages (except P0 and P1) compared to controls.
Conclusions:
- The elevated density of mu-opioid binding sites in the brainstem of IUGR rats provides a potential neurobiological explanation for their increased susceptibility to respiratory disorders.
- These findings suggest that alterations in the opioid system may contribute to the lower Apgar scores and respiratory complications observed in infants with IUGR.
Abstract:
The opioid mu-system is involved in brainstem-mediated respiratory control. Infants with intra-uterine growth restriction (IUGR) have more respiratory disorders in the early postnatal period. Using [(3)H]DAGO, a mu-selective ligand, and a computer-based image analysis of autoradiography, we compared the ontogeny and distribution of mu-opioid binding sites in the brainstem of IUGR and control rats in utero (E21), at birth (P0) and on postnatal days 1 (P1), P7, P10, P14 and P21. The ontogeny pattern was found to be similar in both groups. The density of the binding sites, which was low in E21, increased at P0, slightly declined at P1 and remained relatively constant thereafter. The distribution of DAGO-binding sites, also similar in both groups, was heterogeneous and was much denser in the dorsal areas of medulla and pons. In particular, binding sites were highly concentrated in nuclei involved in the cardio-respiratory function. However, DAGO-binding density was higher at all ages (except for P0 and P1) in IUGR than in control rats. Taken together, these results give at least a partial explanation for the effects of IUGR which lowers the Apgar score at birth and raises the incidence of respiratory disorders in infants.
