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PKC alpha mediates maternal touch regulation of growth-related gene expression in infant rats
Saul M Schanberg1, Vickie F Ingledue, Joanna Y Lee
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. schan003@mc.duke.edu
Insights
Maternal separation in rat pups suppresses growth by disrupting tactile signals, interfering with protein kinase Calpha activation and downstream gene expression essential for development. This highlights the critical role of nurturing touch in neonatal growth.
Area of Science:
- Molecular Biology
- Developmental Neuroscience
- Endocrinology
Background:
- Growth-promoting hormones like prolactin (PRL) and growth hormone (GH) normally increase ornithine decarboxylase (ODC) gene expression in rat pups.
- Maternal separation (MS) disrupts sensory signals, suppressing the expected increase in ODC gene expression.
Purpose of the Study:
- To identify the molecular mechanism by which maternal separation (MS) inhibits ODC gene expression.
- To elucidate how tactile stimuli from the mother regulate ODC biosynthesis and neonatal growth.
Main Methods:
- Investigated the impact of maternal separation on PRL-evoked ODC gene expression in rat pups.
- Examined the role of sn-1,2-diacylglycerol (DAG) and protein kinase Calpha (PKCalpha) signaling pathways.
- Assessed the expression of c-myc and max mRNA, known transactivators of the ODC gene.
Main Results:
- Maternal separation (MS) limits PRL-stimulated ODC biosynthesis by interfering with DAG activation of PKCalpha.
- This signaling disruption consequently affects c-myc and max mRNA expression.
- PKCalpha activation by DAG is identified as a critical control point regulated by tactile stimuli.
Conclusions:
- Nurturing touch, mediated by tactile stimuli, is crucial for activating PKCalpha and regulating ODC gene expression necessary for neonatal growth and development.
- Disruption of mother-infant tactile interactions can lead to maladaptive growth consequences, as seen in premature infants.
- Understanding this mechanism offers potential therapeutic targets for children experiencing failure-to-thrive.
Abstract:
During short-term periods of separation of rat pups from their mothers, the loss of certain sensory signals suppresses the increase in ornithine decarboxylase (ODC) gene expression induced by the growth-promoting hormones prolactin (PRL) and growth hormone (GH). Here, we identify a molecular mechanism through which maternal separation (MS) curtails ODC expression. Our results demonstrate that the absence of specific tactile stimuli provided by the mother limits PRL-evoked stimulation of ODC biosynthesis by interfering with sn-1,2-diacylglycerol's (DAG) ability to activate protein kinase Calpha (PKCalpha) and consequently c-myc mRNA and max mRNA expression. The proteins encoded by these proto-oncogenes function as direct transactivators of the ODC gene. As ODC activity is obligatory for normal cell replication and differentiation, PKCalpha activation by DAG represents an important control point at which 'nurturing touch' regulates growth and development of the neonate. Such a mechanism can explain the maladaptive consequences of disrupting mother-infant tactile interactions as occurs in isolated premature babies. Also, it could provide a basis for developing therapeutic interventions to maximize growth potential in children failing-to-thrive despite normal maternal care.
