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Published on: November 20, 2015
Fetal and postnatal development of cyclic GMP phosphodiesterase activity in the rat brain
1Servicio de Bioquímica, Departamento de Investigación, Centro "Ramón y Cajal," Madrid, Spain.
Insights
Cyclic GMP phosphodiesterase activity in developing rat brains shows significant changes, peaking in specific regions postnatally. This enzyme
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Cyclic guanosine monophosphate (cGMP) is a crucial second messenger in the central nervous system.
- Cyclic GMP phosphodiesterase (cGMP PDE) regulates intracellular cGMP levels by catalyzing its hydrolysis.
- Understanding cGMP PDE developmental changes is vital for comprehending brain maturation and function.
Purpose of the Study:
- To investigate the developmental profile of cyclic GMP concentration and cGMP PDE activity in the rat brain.
- To analyze changes from late fetal stages through postnatal development into adulthood.
- To explore regional differences in cGMP PDE activity during brain development.
Main Methods:
- Measurement of cyclic GMP concentration and cGMP PDE activity in various brain regions of rats at different developmental time points (fetal and postnatal).
- Kinetic analysis of the enzyme, including Vmax and apparent Km, during postnatal forebrain development.
- Comparison of enzyme activity across different brain structures (limbic system, corpora striata, cerebral hemispheres, diencephalon, cerebellum).
Main Results:
- Cyclic GMP concentration increased gradually, reaching adult levels by 15 days postpartum.
- cGMP PDE activity showed a transient decrease in late-term fetuses and neonates, potentially linked to parturition.
- Postnatal development revealed parallel increases in cGMP PDE activity in forebrain regions, peaking around 20-30 days.
- Cerebellar cGMP PDE activity was exceptionally high in 4-day-old rats, decreasing significantly by 10 days.
- Kinetic analysis indicated increased Vmax and apparent Km during postnatal forebrain development, except for a decreased Vmax in the cerebellum.
Conclusions:
- Rat brain development involves dynamic regulation of cGMP PDE activity, with distinct temporal and regional patterns.
- The observed changes in cGMP PDE activity likely play a significant role in modulating cGMP signaling during neural maturation.
- Fetal endocrine preparation for parturition may influence early cGMP PDE activity changes.
Abstract:
Cyclic GMP concentration and cyclic GMP phosphodiesterase activity were studied in rat mothers and fetuses at 17, 19 and 21 days of intrauterine life and 0, 1, 4, 10, 15,20, 30 and 45 days after birth. During this developmental period, the increase in cyclic GMP concentration was discrete and the value in 15-day-old rats was already similar to the adult level. Cyclic GMP phosphodiesterase activity increased from 17- to 19-day fetuses and was significantly reduced in 21-day fetuses, neonates, and 1-day-old rats. This reduction may be a result of fetal endocrine preparation for parturition. During postnatal development, cyclic GMP phosphodiesterase activity increased in a parallel way in the limbic system, corpora striata, cerebral hemispheres, and diencephalon, reaching maximal level between 20 and 30 days after birth, and then decreasing to the adult value. The highest activity was found in corpora striata and the lowest in diencephalon. Cerebellar cyclic GMP phosphodiesterase activity was very high in the 4-day-old rat (257% of adult value) and diminished significantly in the 10-day-old rat with no subsequent changes. Kinetic analysis of the enzyme during postnatal forebrain development showed an increase in both the V(max) and the apparent K(m). A decrease in the enzyme's V(max) was observed only in the cerebellum. The importance of cyclic GMP phosphodiesterase regulation of cyclic GMP concentrations in the brain during development is discussed.
