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Effects of beta-endorphin on DNA synthesis in brain regions of preweanling rats
B A Lorber1, S K Freitag, J V Bartolome
1Department of Pharmacology, Duke University Medical Center, Durham, NC 27710.
Abstract:
Recent studies of whole brain in rat pups have shown a marked decrease in DNA synthesis following intracisternal (i.c.) administration of beta-endorphin (BE). This investigation examines DNA synthesis in the cerebral cortex and cerebellum to determine whether the effect shows regional selectivity. Two- to twenty-day-old rats were given a single ic injection of BE, and DNA synthesis was assessed 1 h later. In the cerebral cortex, a region that undergoes major phases of cell multiplication in the immediate pre- and postnatal periods, BE significantly decreased DNA synthesis in 2-day-old rats, and a maximal inhibition was obtained by 4 days of age. In contrast, the cerebellum, a region that grows predominantly after birth, showed less sensitivity to BE during the early postnatal days, and a maximal effect was not attained until 10 days of age. While at 15 days of age the inhibition began to diminish in the cortex, a maximal effect was still seen in the cerebellum. Naloxone prevented the response in both brain regions, indicating the participation of opioid receptors. These results indicate that CNS BE is apparently able to alter DNA synthesis throughout the brain, with the greatest sensitivity occurring in those regions with highest mitotic rates at the time of exposure to BE.
Insights
Beta-endorphin (BE) significantly reduces DNA synthesis in developing rat brains, with effects varying by brain region and age. Naloxone blocks this response, indicating opioid receptor involvement in brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Previous studies indicated beta-endorphin (BE) decreases DNA synthesis in the whole rat pup brain.
- The regional selectivity of this effect across different brain regions and developmental stages was not fully understood.
Purpose of the Study:
- To investigate the regional selectivity of beta-endorphin's effect on DNA synthesis in the cerebral cortex and cerebellum of developing rats.
- To determine the age-dependent sensitivity of these brain regions to beta-endorphin.
- To confirm the involvement of opioid receptors in this process.
Main Methods:
- Intracisternal (i.c.) administration of beta-endorphin (BE) to rats aged 2 to 20 days.
- Assessment of DNA synthesis in the cerebral cortex and cerebellum 1 hour post-injection.
- Administration of naloxone to assess opioid receptor involvement.
Main Results:
- BE significantly decreased DNA synthesis in the cerebral cortex of 2-day-old rats, with maximal inhibition by day 4.
- The cerebellum showed less sensitivity in early postnatal days, with maximal inhibition observed at 10 days of age.
- Naloxone administration prevented the inhibitory effects of BE in both brain regions, confirming opioid receptor mediation.
Conclusions:
- Central nervous system beta-endorphin can alter DNA synthesis across various brain regions.
- The sensitivity to BE's effect on DNA synthesis is highest in regions with the greatest mitotic activity at the time of exposure.
- Opioid receptors play a crucial role in mediating beta-endorphin's impact on brain development and DNA synthesis.