Interleukin-2 receptors and interleukin-2-mediated signaling in myelin: activation of diacylglycerol kinase and phosphatidylinositol 3-kinase.

Myelin was previously shown to possess neurotransmitter and cytokine receptors that trigger well-defined signaling mechanisms within the multilamellar structure. The present study reveals the presence of an interleukin-2 (IL-2) receptor in isolated mouse CNS myelin that responds to recombinant mouse IL-2 by activating diacylglycerol kinase (DAGK) and phosphoinositide 3-kinase (PI3K); additional evidence suggests participation by protein tyrosine kinase. Activation of myelin DAGK by IL-2 occurred in brain stem tissue mince and was blocked by chelerythrin chloride, indicating an essential role for myelin-localized protein kinase C. Two inhibitors of PI3K, wortmannin and LY294002, blocked endogenous PI3K as well as that enhanced by IL-2. Activation of PI3K by IL-2 was also blocked by tyrphostin A25, a selective inhibitor of PTK, suggesting activation of the latter by IL-2 is upstream to PI3K activation. This reaction resulted in tyrosine phosphorylation of a protein tentatively identified as the p85 subunit of PI3K. Developmental changes were noted in that receptor density and signaling activity were robust during the period of rapid myelination and declined rapidly thereafter.

The phosphoinositide signaling cycle in myelin requires cooperative interaction with the axon.

Previous studies on the origin of myelin phosphoinositides involved in signaling mechanisms indicated axon to myelin transfer of phosphatidylinositol followed by myelin-localized incorporation of axon-derived phosphate groups into phosphatidylinositol 4-monophosphate and phosphatidylinositol 4,5-bisphosphate. This is in agreement with other studies showing the presence of phosphorylating activity in myelin that converts phosphatidylinositol into the mono-and diphospho derivatives. It was also found that the second messenger, inositol 1,4,5-trisphosphate, is hydrolyzed to inositol 1,4-bisphosphate by a myelin-localized enzyme. The present study was undertaken to determine the locus of the remaining reactions leading to formation of free inositol and completion of the cycle by resynthesis of phosphatidylinositol. The latter reaction was found to occur preferentially in isolated axons, and to a limited extent if at all in myelin. On the other hand, hydrolytic reactions which sequentially convert inositol 1,4,5-trisphosphate to inositol 1,4-bisphosphate, inositol 1-phosphate, and free inositol were found to occur more prominently in myelin. Thus, restoration of phosphoinositides following signal-induced breakdown of PIP2 in myelin is seen as requiring metabolic interplay between myelin and axon.

Myelin contains neutral sphingomyelinase activity that is stimulated by tumor necrosis factor-alpha.

Purified myelin from mouse brain was found to contain two forms of neutral sphingomyelinase, one Mg2+ dependent and the other Mg2+ independent. The former had a pH optimum of 7.5 and Km of 0.35 mM, whereas the corresponding values for the latter were pH 8.0 and Km 3.03 mM. Specific activity of the Mg(2+)-dependent enzyme showed a rostral-caudal gradient, ranging from 75 nmol/mg protein/hr in myelin from cerebral hemispheres to 21 nmol/mg protein/hr in myelin from spinal cord. Relative specific activity was approximately 20% that of brain stem or cerebral hemisphere homogenate. Treatment of myelin with taurocholate or high salt concentration did not significantly reduce activity of the Mg(2+)-dependent enzyme. The activity of that enzyme did not change with time or in the presence or absence of protease inhibitors; by contrast, that of Mg(2+)-independent enzyme decreased sharply in the absence of protease inhibitors but rose in their presence. To test for the effect of tumor necrosis factor-alpha (TNF alpha) on myelin sphingomyelinase, mouse brain myelin was labeled in vivo by intracerebral injection of [3H]acetate into 18-20-day-old mice. After 40 hr, brain stems were removed, minced, and treated with TNF alpha in Krebs-Ringer solution, after which myelin was immediately isolated. Separation and counting of individual lipids revealed TNF alpha treatment to cause increased labeling of myelin ceramide and cholesterol ester with concomitant decrease in myelin sphingomyelin. Western blotting of myelin proteins using antibodies to the two TNF alpha receptors as probes revealed the presence of the p75 receptor. Implications of these findings in relation to possible mechanisms of autoimmune demyelination are discussed.

Reciprocity in mother-infant vocal interactions: relationship to the quantity of mothers' vocal stimulation.

A study of 147 mother-infant dyads revealed that the most talkative mothers did not allow their infants to initiate many conversations. The least talkative mothers ignored many of their infants' vocalizations. Mothers in the mid-level talking range demonstrated the greatest reciprocity, allowing their infants to initiate more conversations.

Planned conception and infant functioning at age three months: a cross-cultural study.

The conceptions of 53 American and 54 Greek infants were categorized as planned or unplanned on the basis of mothers' reports. At age three months in both cultural groups, infants in the planned category showed higher levels of cognitive processing and attachment to their mothers than did infants in the unplanned category, as shown by their differential vocal responses to mothers versus a female stranger.

PIP: Female investigators observed 107 full-term, normal, home-reared, 3-month-old infants in their homes with their mothers present to determine whether the babies whose mothers planned their pregnancy had a higher differential vocal response to their mothers than to a female stranger than did babies whose mothers did not plan their pregnancy. They compared the reactions of 53 infants from Los Angeles, California, with those of 54 infants from Athens, Greece. Regardless of culture, infants who were a result of a planned pregnancy had a higher differential vocal response score and vocalized significantly more in response to their mothers than to the stranger than did infants who were the result of an unplanned pregnancy (p .01 and .001, respectively). These findings demonstrated the 3-month-old infant's cognitive capacity to differentiate the mother from the stranger and their preference for their mother. They also suggested that the mother's feelings toward the baby do indeed contribute to the quality of the relationship and the degree of reciprocity with the mother. Further, it appears that children whose conception is unplanned are at greater risk for maternal rejection and subsequent psychopathology than children whose conception is planned. Thus, psychologists and psychiatrists should study the degree of bonding between mother and child and, if required, try to strengthen the bonding in cases where the mother did not plan the child's conception and psychopathology exists.

Differential functioning on the Illingworth by home- vs institution-reared 3-month-old infants.

The performance on the Illingworth of 32 3-mo.-old home-reared Greek infants was compared to that of 22 infants reared in a modern institution. Home-reared infants were superior to institutional infants in every aspect of development except on Manipulations (fine motor coordination). It is speculated that the superiority of the home infants is attributed to the quality of the mother/caretaker-infant relationship.

Parental influences on the development of adolescent autonomy and identity.

Two studies were undertaken to examine parental influences on autonomy and identity development. In Study 1, 262 adolescents in seventh and eleventh grades were given Kurtines's autonomy measure, Simmons's identity measure, and Elder's questions regarding the adolescents' perceptions of their parents' autocratic, democratic, or permissive parenting styles. Study 2 was a replication with 168 subjects. Across both studies it was found that sex-role socialization is more influential for automony development than is either level of parental power or age. Both age and father's use of democracy were the most influential variables on identity development.