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Biomedical subjects

Saul M Schanberg

Publications and source records attributed to Saul M Schanberg.

2 recordsLinked to original sources

PKC alpha mediates maternal touch regulation of growth-related gene expression in infant rats.

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.

Animals↗

Serotonin-related gene polymorphisms and central nervous system serotonin function.

Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.

Adult↗