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J A Kessler

Publications and source records attributed to J A Kessler.

140 records · Page 8Linked to original sources
PubMed1981

Transmitter phenotypic expression in the embryo.

The initial appearance and development of noradrenergic and adrenergic phenotypic characters was studied in the rat embryo by immunocytochemical methods. Tyrosine hydroxylase and dopamine-beta-hydroxylase (noradrenergic enzymes) appeared at 11.5 days of gestation (Day E 11.5; 27-30 somites) in sympathetic ganglion primordia and in cells of the gut. While tyrosine hydroxylase and dopamine beta-hydroxylase immunoreactivity increased progressively in ganglion primordia, the enzymes disappeared in the gut cells after E 13.5. However, the gut cells themselves persisted, as indicated by the high-affinity uptake of noradrenaline (norepinephrine). Consequently, initial appearance of noradrenergic characters does not ensure persistence and subsequent development, indicating that early phenotypic expression is a mutable process. This contention was supported by the observations that pharmacological stress of pregnant rats in the form of reserpine, or treatment with glucocorticoids, prolonged the appearance of catecholamines in the gut cells. Thus, maternal-embryonic relations in general, and maternal glucocorticoids in particular, may influence embryonic phenotypic expression. Treatment of embryos with nerve growth factor also prolonged the appearance of noradrenergic characters in the gut cells. Expression of the adrenergic phenotype was apparently regulated differently from noradrenergic expression, since phenylethanolamine-N-methyltransferase (PNMT), the adrenaline-(epinephrine)-synthesizing enzyme, was undetectable in ganglion primordia and gut cells. PNMT initially appeared at E 17.5 in cells which had migrated to be adrenal anlage. Extensive studies suggest that the initial appearance of PNMT occurs independently of glucocorticoid regulation, while subsequent development is dependent on corticoids.

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PubMed1981

Similarities in development of substance P and somatostatin in peripheral sensory neurons: effects of capsaicin and nerve growth factor.

Development of the two putative peptide neurotransmitters, substance P (SP) and somatostatin (SS), were compared in rat dorsal root ganglion (DRG) and spinal cord in vivo. The content of SS in the sixth cervical DRG increased 5-fold during the first 5 weeks of life, rising from 24 pg per ganglion at birth. SP content increased 4.5-fold during the first 5 weeks, from 56 pg per ganglion at birth. The developmental profiles for these two peptides were virtually parallel, suggesting that their respective neuronal populations developed in synchrony. Treatment with nerve growth factor (NGF) significantly increased the content of both SP and SS in the DRG and dorsal spinal cord. Conversely, treatment with capsaicin significantly decreased both SP and SS in the DRG and dorsal spinal cord. Consequently, experiments involving NGF or capsaicin treatment of sensory neurons must be interpreted with extreme care, because specificity is not limited to a single peptide phenotype. Although the mechanisms of action of NGF and capsaicin on SP and SS have not been defined, the similarity of the responses of the two peptides suggests that their development may be regulated by similar processes.

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PubMed1980

The effects of nerve growth factor (NGF) and antiserum to NGF on the development of embryonic sympathetic neurons in vivo.

The role of nerve growth factor (NGF) in the development of embryonic sympathetic neurons was examined in vivo. Individual mouse embryos received transuterine injections of NGF or antiserum to NGF (anti-NGF), and the effects on the superior cervical ganglion (SCG) were studied. Treatment with NGF at any gestational stage, from the time of ganglion aggregation to birth, increased ganglion tyrosine hydroxylase (T-OH) activity. Both the number of catecholaminergic neurons and T-OH activity per neutron were increased. Choline acetyltransferase (ChAc) activity was increased by NGF at early gestational stages, but not at later stages. These observations suggest that perikarya containing ChAc are responsive to NGF, whereas preganglionic nerve terminals are not. Treatment with anti-NGF rapidly and permanently decreased ganglion T-OH activity. The effects of anti-NGF were more pronounced at later gestational stages, suggesting that ganglia become increasingly dependent on NGF during development. Alteration of maternal levels of NGF had no effect on development of the embryonic SCG, suggesting that local embryonic concentrations of NGF are responsible for modulating sympathetic ontogeny.

Aging↗
PubMed1980

Nerve growth factor stimulates the development of substance P in sensory ganglia.

The development of the putative neurotransmitter substance P (SP) in rat dorsal root ganglion (DRG) was defined in vivo. The sixth cervical DRG of newborn rats contained 70 pg of SP, and the ganglionic content increased 5.5-fold during the first 5 weeks of life. Forelimb amputation partially prevented the normal developmental increase of SP in the sixth cervical DRG destined to innervate that limb. Conversely, treatment with nerve growth factor (NGF) increased both ganglionic SP and total ganglion protein. Moreover, NGF administration prevented the failure of SP development that followed amputation, suggesting that NGF may mediate the limb-DRG interaction. However, treatment with antiserum to NGF failed to significantly inhibit development of ganglion SP. Consequently, neonatal ganglia may remain responsive to NGF, without requiring the protein for survival. SP appears to be an excellent index of the maturation of neurons in dorsal root ganglia.

Age Factors↗
PubMed1979

The role of axonal transport in the regulation of enzyme activity in sympathetic ganglia of adult rats.

The relationship of perikaryal and presynaptic enzyme activity to axonal transport was studied in adult sympathetic neurons in the rat superior cervical ganglion (SCG). Surgical axotomy or local colchicine application to the postganglionic nerves resulted in a significant decrease in ganglionic tyrosine hydroxylase (T-OH) activity without a significant alteration in choline acetyltransferase activity. Colchicine did not appear to block axonal impulse conduction since pupillary and eyelid function remained normal. Consequently, the reduced T-OH activity resulted from alteration of other axonal functions. Axotomy or colchicine application decreased T-OH activity in decentralized ganglia, suggesting that the depression of perikaryal T-OH was not secondary to altered orthograde transsynaptic interactions. Colchicine did not prevent transsynaptic induction of T-OH by reserpine, suggesting that axonal transport is not necessary for enzyme induction. Nerve growth factor (NGF) treatment partially prevented the effects of colchicine application. It is concluded that in adult sympathetic neurons both orthograde transsynaptic mechanisms and the retrograde transport of NGF normally govern perikaryal T-OH activity.

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PubMed1976

Transport of 5-hydroxy-3-indoleacetic acid by spinal cord during subarachnoid perfusion.

The transport of [14C]5-hydroxy-3-indoleacetic acid (5-HIAA) by the spinal cord was investigated with spinal subarachnoid perfusions of 20 rhesus monkeys. For spinal white matter, [14C]5-HIAA was found to distribute in a tissue space of 50-55% and to exchange readily between tissue and blood across parenchymal capillaries. The data were analyzed with a model of the spinal cord as a cylinder and a mean capillary transfer half-time of 20 min determined. The spinal cord cleared [14C]5-HIAA from 19 mul/min of CSF. Administration of probenecid yielded a somewhat lower mean tracer clearance rate (14 mul/min) but did not alter the capillary exchange half-time or the distribution volume of [14C]5-HIAA in the spinal cord. The data suggest that capillaries within spinal white matter transport 5-HIAA by a mechanism which is insensitive to inhibition by probenecid and that lumbar CSF concentrations reflect only a small portion of total 5-HIAA production by the central nervous system.

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PubMed1976

3-Methoxy-4-hydroxyphenylethyleneglycol (mhpg) transport from the spinal cord during spinal subarachnoid perfusion.

Spinal subarachnoid perfusions of rhesus monkeys were performed to study the transport of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) by the spinal cord. The perfusate contained [3H]MHPG and a reference extracellular space marker ([14C]sucrose of [14C]ethylenediaminetetraacetic acid-calcium complex). The mean (+/- S.D.) clearance of MHPG by the monkey spinal cord was 33 (+/- 4) mul/min. Analysis of serial sections of spinal tissue after each perfusion facilitated determination of several basic parameters of MHPG transport. MHPG has a spinal tissue distribution space of 70-80%. MHPG enters capillaries within spinal tissue throughout the entire spinal cord. The mean capillary exchange half-time was 8.2 min +/- 1.9 min. MHPG crosses cell membranes easily and diffuses through cells rapidly. The apparent tissue diffusion coefficient approximated the diffusion coefficient in water (8.5 x 10(-6) sq.cm/sec). The data suggests that CSF levels of MHPG are an uncertain indicator of norepinephrine metabolism and that lumbar CSF levels of MHPG reflect in large part spinal cord rather than brain metabolism.

Animals↗
PubMed1976

Spinal subarachnoid perfusion of rhesus monkeys.

A technique of spinal subarachnoid perfusion is descirbed which effectively isolates the spinal cord from the remainder of the central nervous system. A method of obtaining and analyzing spinal cord tissue after subarachnoid perfusion is presented. The spinal subarachnoid space of 12 rhesus monkeys was perfused with [14C]sucrose, [14C]ethylenediaminetetraacetic acid-calcium complex (EDTA), and dextran blue as test substances. The sucrose and EDTA spinal cord distribution spaces are 13.6 +/- 0.9% in white matter and 18.1 +/- 1.4% in gray matter. The diffusion coefficient in tissue of sucrose is 1.7 x 10(-6) cm2/s and of EDTA is 1.55 x 10(-6) cm2/s. The spinal cord tortuosity factor is 2.0-2.1. Six rhesus monkeys were infused intravenously with [3H]sucrose and [14C]EDTA; the spinal capillary exchange half-time from blood to extracellular fluid was greater than 6 h for both sucrose and EDTA.

Animals↗
PubMed1976

Homovanillic acid transport by the spinal cord.

Spinal subarachnoid perfusions of rhesus monkeys were performed to study spinal transport of homovanillic acid in control and probenecid-treated animals. Homovanillic acid enters capillaries within spinal tissue throughout the spinal cord. The mean capillary exchange half-time for homovanillic acid was 19.2+/-2.8 minutes; probenecid did not affect this value significantly. Despite its polar nature, homovanillic acid crosses cell boundaries easily and equilibrates in a distribution volume (55 percent) approaching the total water space. The spinal cord clears homovanillic acid from 21+/-4 mul per minute of cerebrospinal fluid. The rate of clearance after probenecid administration was not significantly different. The apparent diffusion coefficient in tissue of homovanillic acid approximated the diffusion coefficient in water (8.0 X 10(-6) cm2 per second). The data show that homovanillic acid is transported by capillaries throughout spinal tissue by a mechanism largely insensitive to inhibition by probenecid. Lumbar cerebrospinal fluid concentrations of homovanillic acid even after probenecid administration therefore reflect only part of the total dopamine metabolism.

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PubMedDate not supplied

Cytokines regulate the cellular phenotype of developing neural lineage species.

The patterns and mechanisms of action of inductive signals that orchestrate neural lineage commitment and differentiation in the mammalian brain are incompletely understood. To examine these developmental issues, we have utilized several culture systems including conditionally immortalized cell lines, subventricular zone progenitor cells and primary neuronal cultures. A neural stem and progenitor cell line (MK31) was established from murine embryonic hippocampus by retroviral transduction of temperature-sensitive alleles of the simian virus 40 large tumor antigen. At the non-permissive temperature for antigen expression (39 degrees C) in serum-free media, the neural stem cells give rise to a series of increasingly mature neuronal progenitor and differentiated cellular forms under the influence of a subset of hematolymphopoietic cytokines (interleukins 5, 7, 9 and 11), when individually co-applied with transforming growth factor alpha, after pretreatment with basic fibroblast growth factor. These cellular forms elaborated a series of progressively more mature neurofilament proteins, a sequential pattern of ligand-gated channels, and inward currents and generation of action potentials with mature physiological properties. Because the factors regulating the development of central nervous system astrocytes have been so difficult to define, we have chosen to focus, in this manuscript, on the elaboration of this cell type. At 39 degrees C, application of a subfamily of bone morphogenetic proteins of the transforming growth factor beta superfamily of growth factors sanctioned the selective expression of astrocytic progenitor cells and mature astrocytes, as defined by sequential elaboration of the Yb subunit of glutathione-S-transferase and glial fibrillary acidic protein. These lineage-specific cytokine inductive relationships were verified using subventricular zone neural progenitor cells generated by the application of epidermal growth factor, alone or in combination with basic fibroblast growth factor, to dissociated cellular cultures derived from early embryonic murine brain, a normal non-transformed developmental population. Finally, application of a different series of cytokines from five distinct factor classes (basic fibroblast growth factor, platelet-derived growth factor-AA, insulin-like growth factor 1, neurotrophin 3 and representative gp130 receptor subunit-related ligands) caused the elaboration of oligodendroglial progenitor species and post-mitotic oligodendrocytes, defined by progressive morphological maturation and the expression of increasingly advanced oligodendroglial and oligodendrocyte lineage markers. In addition, seven different gp130-associated neuropoietic (ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin-M) and hematopoietic (interleukins 6, 11, 12, granulocyte-colony stimulating factor) cytokines exhibited differential trophic effects on oligodendroglial lineage maturation and factor class interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

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