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R G Kalb

Publications and source records attributed to R G Kalb.

40 records · Page 3Linked to original sources

Molecular evidence for early activity-dependent development of hamster motor neurons.

Monoclonal antibody Cat-301 recognizes a surface antigen on subsets of neurons in many areas of the mammalian CNS, including Y-cells in the cat dorsal lateral geniculate nucleus (LGN) and spinal motor neurons in several species. We have shown previously that the Cat-301 antigen is expressed relatively late in postnatal development, with a time course that matches that of late developmental features of both LGN and spinal cord neurons. The developmental time course of the expression of the Cat-301 antigen in the LGN correlates with the period during which visual deprivation can alter LGN Y-cells. Neonatal visual deprivation (by monocular lid suture or dark rearing) suppresses Cat-301 expression on Y-cells, while deprivation in adult animals has no effect on antigen expression. These results suggested that the onset of Cat-301 immunoreactivity provides a positive molecular marker for the end of a critical period in cat visual system development. To determine if Cat-301 might be a general marker for experience-dependent development in other areas of the CNS we have examined antigen expression on hamster spinal cord motor neurons. Here, we report that Cat-301 immunoreactivity develops on hamster motor neurons between postnatal days 7 and 14. Altering neuromuscular activity by sciatic nerve crush or thoracic hemicordotomy inhibits Cat-301 expression on motor neurons if performed before the onset of Cat-301 immunoreactivity. Other motor neuron antigens are unaffected by this procedure. In adult animals, nerve crush or cordotomy has no effect on Cat-301 immunoreactivity, demonstrating that Cat-301 expression is not simply dependent on ongoing neural activity. These observations suggest that motor neurons, like LGN neurons, require some pattern of neuronal activity during a critical period in development and, further, that the phenotypic changes in neurons consequent to early activity are reflected by the expression of specific molecules. The identification and characterization of such molecules may yield a description of the molecular mechanisms of experience-dependent development.

Aging↗

Hormonal regulation of fibrinogen synthesis in cultured hepatocytes.

Most of what was originally known of the effects of hormones on fibrinogen synthesis was based, as noted above, on experiments involving surgical removal of endocrine glands. Some caution should be exercised when using such in vivo experiments to derive the hormonal requirements of fibrinogen synthesis, however, since multiple hormonal alterations often occur in these animals. The development of a variety of ex vivo systems has allowed investigators to more carefully control the hepatocellular environment. The work of several laboratories, including our own, has now made it clear that hormones and other agents directly stimulate hepatocellular synthesis of fibrinogen. From the studies summarized here, using chick embryo hepatocytes as a model, several generalizations emerge: Fibrinogen synthesis may be considered to be a "constitutive" liver function, since hepatocytes cultured without serum, hormones or other macromolecular supplements synthesize this protein at a basal rate for several days. Addition of certain hormones (e.g. T3, dexamethasone, insulin), individually and in physiological concentrations, elicits an increase in fibrinogen production, varying with each agent in onset, dose, minimum exposure required and accompanying effects on the synthesis of other plasma proteins. Glucocorticoids and thyroid hormones are similar in the selectivity of their stimulation (neither affects albumin or transferrin synthesis) but differ in that thyroid hormones need to be present for just a short "triggering" period. The stimulation of fibrinogen synthesis by insulin occurs only following prolonged exposure to concentrations 10-times higher than the very low doses to which albumin synthesis responds rapidly.

Adrenocorticotropic Hormone↗

Immunofluorescence localization of plasma protein synthesis in cultured chick hepatocytes.

Fibrinogen, albumin and the major apoprotein of high density lipoprotein (apoprotein A) were localized in a primary embryonic chick liver cell culture by indirect immunofluorescence staining. Changes in the pattern of plasma protein synthesis under a variety of conditions, as measured by the accumulation of secreted plasma proteins in the culture medium, could be studied at the cellular level because relative fluorescence intensities were shown to reflect synthetic rates. In all cases studied, the immunofluorescence of the hepatic parenchymal cells was of a similar intensity throughout the monolayers, indicating that the cells in culture constitute a homogeneous population with respect to the synthesis of these plasma proteins.

Animals↗

Activity-dependent development of spinal cord motor neurons.

Patterned neuronal activity in early postnatal life can regulate the acquisition of the mature morphological and electrophysiological properties of neurons. Many properties of motor neurons are developmentally regulated and may be influenced by epigenetic factors. The pattern of activation of motor neurons can regulate axon terminal morphology and synaptic efficacy at the neuromuscular junction. Motor neuron morphology and synaptic connections can also be modified by exposure to specific hormones in the early postnatal period. The acquisition of mature physiological and anatomical properties is paralleled by the acquisition of specific molecular properties. Recent experiments using molecular markers for motor neuron differentiation indicate that motor neurons undergo activity-dependent development during a circumscribed period in early postnatal life. Normal motor neuron differentiation requires a normal pattern of neuronal activity in early postnatal life. Differentiation also requires activation of the NMDA receptor over the same time period. The activity-dependent development of morphological, electrophysiological and molecular properties of motor neurons is similar to activity-dependent development in the vertebrate visual system. The neuromuscular system may provide an accessible system for characterizing the molecules subserving the translation of patterned neuronal activity into mature neuronal phenotype.

Animals↗