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Biomedical subjects

J M Lauder

Publications and source records attributed to J M Lauder.

At least 91 records · Page 5Linked to original sources
PubMed1985

Decreased serotonin content of embryonic raphe neurons following maternal administration of p-chlorophenylalanine: a quantitative immunocytochemical study.

Previous studies from this laboratory have suggested that serotonergic (5-HT) neurons may influence the differentiation of their embryonic target cells in the developing rat brain. The present study was designed to determine whether or not maternal p-chlorophenylalanine (pCPA) administration could deplete serotonin (5-HT) in developing 5-HT neurons during embryonic days 13-15, when the effects of pCPA on neuronal genesis have been observed previously. For this study, pCPA was administered to timed-pregnant rats and embryos were sacrificed at two different gestational ages, embryonic days 13-14 (E13-14) and 14-15 (E14-15). Immunotitration experiments were carried out on tissue sections, using an antiserum to 5-HT-hemocyanin conjugates to obtain a relative estimate of the amount of 5-HT contained within individual 5-HT neurons of embryos from pCPA-treated and control mothers. Diminished immunoreactivity as a consequence of addition of increasing amounts of antigen was then quantitated on a relative scale by comparison with the amount of immunoreactivity present when no antigen was added to the primary antiserum. Two major findings resulted from this study: maternal pCPA treatment depleted 5-HT by approximately 50% in developing 5-HT neurons at embryonic ages E13-14 and E14-15, but depletion appeared to be greatest in the youngest embryos; developing 5-HT neurons increased their content of neurotransmitter by approximately 10-fold during this one day of embryonic development, an effect which could be observed in both pCPA-treated and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

pp60c-src in the developing cerebellum.

pp60c-src was localized in the cerebellum of developing chicken embryos by immunoperoxidase staining with antisera raised against bacterially expressed pp60v-src. Immunoreactivity (IR) appeared in the cerebellum of the chicken embryos at the time of neuronal differentiation. pp60c-src IR was detected in regions of the developing cerebellum where processes of developing neurons and glia are located. In the early embryo (stage 17), pp60c-src IR was localized in the marginal zone of the cerebellar plate. By stage 40, pp60c-src IR was localized in the process-rich molecular layer of the cerebellum and between the cells of the developing internal granular layer. Cell bodies of cerebellar neurons did not show pp60c-src IR at any stage of development. Mitotically active neuroepithelial cells of the metencephalon did not express pp60c-src before the onset of differentiation in the early embryo, nor did proliferating cells of the external granular layer express pp60c-src at later stages. Although it is not possible to ascertain whether pp60c-src is localized in developing neurons or glia at the light microscope level, the time of its appearance and pattern of distribution in the molecular layer is suggestive of a localization within the developing neuronal processes which compose the bulk of this layer. Biochemical analyses of pp60c-src in the developing cerebellum by the immune complex protein kinase activity and sensitivity of the kinase to inhibition by P1,P4-di(adenosine-5')tetraphosphate confirmed that the expression of pp60c-src coincided with the time of neuronal differentiation. We conclude from these results that in the central nervous systems, pp60c-src may be more important in an aspect of cell differentiation or a mature neuronal function than in the proliferation of neuronal or glial precursors.

Animals↗
PubMed1985

Roles for neurotransmitters in development: possible interaction with drugs during the fetal and neonatal periods.

In conclusion, a variety of experimental evidence suggests roles for serotonin and the catecholamine neurotransmitters in key phases of nervous system development, such as neural-tube formation, proliferation of neuronal precursor cells, and gliogenesis. This raises the possibility that psychoactive drugs of use and abuse which act via these neurotransmitters could, if taken by a woman at an appropriate stage of pregnancy, influence the developing embryonic nervous system by interfering with the synthesis, uptake, or metabolism of these compounds during critical periods of neural ontogeny.

Abnormalities, Drug-Induced↗
PubMed1984

Early postnatal administration of 5,7-DHT: effects on serotonergic neurons and terminals.

Serotonergic neurons throughout the brain were destroyed by early postnatal treatment of rats with an intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT), as demonstrated with biochemical measurements of serotonin and immunocytochemical localization of serotonin-containing neurons. Using these methods, it was shown that approximately 75-98% of serotonergic neurons underwent cell death in rats which were treated on day 3. In contrast, intracisternal administration of 5,7-DHT in adult rats led to the loss of distal serotonergic terminals without apparent loss of the cell bodies. Desipramine pretreatment prevented significant effects of 5,7-DHT on noradrenergic neurons.

5,7-Dihydroxytryptamine↗
PubMed1984

Immunocytochemical localization of glucocorticoid receptors in midgestation murine embryos and human embryonic cultured cells.

Glucocorticoid receptors have been localized immunocytochemically in the developing mouse secondary palatal shelves and in cultured human embryonic palatal mesenchyme cells. In the midgestation embryo, receptors are found in the highest concentration in the palatal mesenchymal cells, suggesting that they play a major role in normal development as well as in glucocorticoid-induced cleft palate. The presence of these receptors in cultured human embryonic palatal cells also suggests that development of the human secondary palate may be dependent on glucocorticoids.

Animals↗
PubMed1984

Optimization of tyrosine hydroxylase immunocytochemistry in paraffin sections using pretreatment with proteolytic enzymes.

Immunocytochemical localization of tyrosine hydroxylase (TH) was performed on paraffin sections pretreated with various proteolytic enzymes. It was found that pretreatment with trypsin (1.2 mg/ml) for 5 min resulted in a dramatic increase in the number of TH-positive terminals throughout the brain, especially in the cerebellum, which contains fine preterminal and terminal axons that are difficult to stain. This pretreatment also led to a significant reduction in background staining and allowed for the use of the TH antiserum at high working dilutions. Several other proteolytic enzymes were tested and only chymotrypsin was nearly as effective as trypsin with respect to TH staining.

Animals↗
PubMed1983

Adult age destruction versus neonatal age destruction of the serotonin system: two models to investigate the survival of serotonin neurons transplanted in adult rats.

Mesencephalic raphe nuclei were transplanted via the cisterna magna in the IVth ventricle of adult rats having received either a neonatal or an adult age destruction of the serotonin system. In neonatally treated rats both serotonin (5-HT) and glial fibrillary acidic protein (GFA) immunocytochemistry showed an absence of survival of 5-HT neurons in the transplants. However, many 5-HT immunoreactive cell bodies and processes were detected in 10-month-old transplants in adult treated animals. These results suggest that recognition processes between the target tissue and the implant may be a prerequisite for the survival of grafted neurons.

Age Factors↗
PubMed1983

Hormonal and humoral influences on brain development.

This review discusses evidence for neurotransmitters as developmental signals in such ontogenic processes as neural tube formation (neurulation), germinal cell proliferation, and neuronal and glial differentiation during brain organogenesis, as well as evidence for other roles of these neurotransmitters in non-neuronal tissues of vertebrates and invertebrates. Evidence also is presented for hormonal regulation of brain development during postnatal neurogenesis and for interrelationships which may link neurotransmitters and hormones in a humoral milieu, providing a variety of control mechanisms for the central and peripheral nervous system during key phases of their development. Given the evidence for neurotransmitters and hormones as coordinating influence on neural ontogeny, it is possible that drugs, stress, and environmental influences may have the ability to perturb particular aspects of these developmental systems if present during those "critical periods" when such humoral influences are important for normal ontogeny.

Adrenal Cortex Hormones↗
PubMed1983

Development of the serotonergic system in the rat embryo: an immunocytochemical study.

The development of central serotonergic neurons has been examined immunocytochemically utilizing an antiserum to serotonin (5-HT). Cells of the B4-B9 complex are first detected early on embryonic day 13 (E13; 7 mm crown rump length, CRL) and increase rapidly in number through E15 when they appear as bilateral columns situated from just caudal to the mesencephalic flexure to the pontine flexure. Aggregation of cells into subgroups is apparent soon after 5-HT neurons leave the ventricular zone, allowing the identification of certain subdivisions of the B4-B9 complex long before they assume their adult locations. The initial detection of 5-HT immunoreactive cells in the medulla occurs 1-2 days after the appearance of cells in the B4-B9 complex, although it has been reported that the time of origin of medullary raphe neurons (B1-B3) occurs before that of raphe neurons in the midbrain and pons (B4-B9). The first medullary 5-HT neurons, comprising the B3 subdivision occur ventro-laterally on E14 (10-11 mm CRL) at least 1-2 days before midline 5-HT neurons are visualized in the B1 and B2 groups. Thus, in contrast to cells in the B4-B9 complex, medullary 5-HT neurons complete much of their migration before they can be detected immunocytochemically, indicating that the time of onset of transmitter synthesis and storage may differ during differentiation of cells sharing a common neurotransmitter phenotype. The formation of ascending 5-HT fiber projections occurs rapidly from cells of the B4-B9 complex. Within 24 hours after the initial detection of 5-HT fiber immunoreactivity in such cells at E13, their axons are seen entering the caudal diencephalon (E14). These fibers have traversed the diencephalon and floor of the telencephalon by E15-E16 and reach the frontal neocortical pole by E17. The main ascending bundle of 5-HT axons courses through the diencephalon in the vicinity of the medial forebrain bundle, although some fibers also diverge and travel along certain pre-existing non-5HT pathways. However, examples are also found of acute directional changes in 5-HT fiber growth which do not appear to be associated with pre-formed non-5HT pathways. The pattern of ascending fiber outgrowth suggests a priority routing system which provides certain regions with 5-HT axons in a preferential sequence irrespective of the distance of these areas from 5-HT cell groups or from major bundles of ascending 5-HT fibers.

Afferent Pathways↗
PubMed1982

Cytosol glucocorticoid binding in monoaminergic cell groups.

The following nuclei containing monoaminergic neurons were punched out from frozen sections of rat brain: locus coeruleus, dorsal raphe nucleus, medial raphe nucleus, and substantia nigra zona compacta. Cytosol preparations from the dissected tissues were examined for 3H-corticosterone binding. Only the locus coeruleus showed a substantial level of 3H-corticosterone binding. No binding capacity was found in cytosols from the raphe nuclei and the substantia nigra. The cytosol steroid binding of the locus coeruleus was determined developmentally. The binding capacity was found to remain virtually unchanged from postnatal day 5 (the earliest period examined) to adulthood. It is possible that a cytoplasmic glucocorticoid receptor may be present in the noradrenergic neurons of the locus coeruleus. Since 3H-corticosterone binding is absent in the raphe nuclei and substantia nigra, biochemical mechanisms involving a glucocorticoid-receptor interaction directly in these serotonergic and dopaminergic neurons may be ruled out.

Animals↗
PubMed1981

3H-thymidine long survival autoradiography as a method for dating the time of neuronal origin in the chick embryo: the locus coeruleus and cerebellar Purkinje cells.

Contrary to previous assumptions, we have found that a single dose of 3H-thymidine (25 muCi), injected into the yolk sac of White Leghorn chick eggs on 2 days of incubation (d.i.) only remains available for DNA-synthesizing (proliferating) cells for 48 hours following the time of injection. This finding now makes it possible to date the time of neuronal origin in the avian embryo using a single injection of isotope and a long survival time (30 days posthatch) as in mammalian studies where 3H-thymidine is only available as a short "pulse." Using this method, we have determined that neurons in the chick locus coeruleus (LC) cease proliferation on 2-6 d.i. with a peak of neuronal genesis on 3-5 d.i. In addition, neuronal genesis is not homogeneous throughout the LC cell population, but occurs in a predominantly caudorostral gradient. Conversely, the cerebellar Purkinje cells cease division on 3-8 d.i. with a peak of heavy labeling on 4-6 d.i., 1 day later than that observed in the LC.

Animals↗
PubMed1981

The immunocytochemical localization of serotonergic neurons in the rat hypothalamus.

In rats pretreated with pargyline and L-tryptophan a group of neurons in the dorsomedial hypothalamus stained immunocytochemically for serotonin. These neurons measured approximately 9 micrometer and were distributed over a rostro-caudal distance of 900 micrometer. There were a total of 708 cells. No labeled cells were seen in this hypothalamic group in normal, colchicine- or pargyline-pretreated rats.

Animals↗
PubMed1981

Development and aging of noradrenergic cell bodies and axon terminals in the chicken.

Tyrosine hydroxylase activity was measured in the region of locus coeruleus, cerebellum, cervical spinal cord, lumbar sympathetic ganglia, and iris throughout most of the life span of the chicken (8 days of incubation to 5 years) to compare developmental trends in tyrosine hydroxylase activity in noradrenergic cell bodies and in axon terminals in both the central and peripheral nervous system. Fluorescence histochemistry and retrograde transport of horseradish peroxidase were used to characterize further the coeruleo-cerebellar projections. Tyrosine hydroxylase activity was detected in the cerebellum as early as 8 days of incubation, which is the earliest stage so far reported. The greatest increase in total tyrosine hydroxylase activity in the region of the locus coeruleus and cerebellum occurred during the embryonic period. There was a more pronounced increase in the cerebellum than in the locus coeruleus region. This is in contrast to the cervical spinal cord where tyrosine hydroxylase activity increased at approximately the same rate during the embryonic and post-hatching periods. Moreover, the cerebellum and cervical spinal cord, two locus coeruleus target sites, displayed different trends in tyrosine hydroxylase activity throughout development and aging. In both structures examined in the peripheral nervous system, the greatest increase in total tyrosine hydroxylase activity occurred during the post-hatching period, with a greater rise in the cell bodies of the lumbar sympathetic ganglia than in the noradrenergic terminals of the iris. In both the central and peripheral nervous system, total tyrosine hydroxylase activity continued to increase in noradrenergic terminals long after hatching reaching the highest levels at 7 months when the chicken is considered fully mature. During aging, 16 months to 5 years, there was a greater decrease in total tyrosine hydroxylase activity in the terminals of noradrenergic neurons than in the cell bodies in both the central and peripheral nervous system, a phenomenon that was more marked in the peripheral nervous system than in the brain.

Aging↗
PubMed1981

Roles for serotonin in neuroembryogenesis.

Possible non-transmitter roles for 5-HT in different phases of early neuroembryogenesis have been discussed based upon experimental evidence from the rat and chick. Fluorescence histochemical studies have demonstrated sites of uptake and synthesis of 5-HT in the chick embryo during the first few days of incubation. These sites are located in discrete regions of the notochord and floor plate of the neural tube as well as in extra-neural regions such as the somites and primitive gut. The 5-HT patterns are distinctly different from those observed for the uptake and synthesis of norepinephrine in embryos of the same age. Spatio-temporal changes in the distribution of these sites during closure of the neural tube suggest a role for 5-HT in various aspects of neural tube development. Moreover, the non-overlapping localization of 5-HT and norepinephrine raises the possibility that these two amines may exert different and perhaps cooperative influences on early neurogenic processes in the chick. In the rat, autoradiographic and biochemical studies concerning the consequences of 5-HT depletion in the embryo for development of different brain regions have provided evidence that 5-HT acts as a "differentiation signal" regulating the time of neuronal genesis in those cell populations which will eventually receive 5-HT innervation. Although the details of this system are as yet unknown, these studies suggest that 5-HT (and possibly the other monoamine transmitters) may actually "mold" the construction of their own circuitry during neurogenesis. Further, the ability of drugs and stress to interact with this process during that period of gestation when the monoamines are required as humoral signals suggests that maternal influences can interfere with ontogeny of this circuitry during pre- and possibly postnatal development. It is not yet clear whether the data in chicks and rats can be directly analogized from the one species to the other. Nevertheless, the evidence that sites of 5-HT uptake and/or synthesis are present during the earliest phases of neurogenesis in the chick and the observation that 5-HT depletion can alter the time of genesis of 5-HT target cells in the rat provide a new context for the consideration of possible actions of 5-HT prior to its role as a neurotransmitter substance.

Animals↗
PubMed1981

Fetal raphe and hippocampal transplants into adult and aged C57BL/6N mice: a preliminary immunocytochemical study.

Fetal mouse raphe and hippocampal tissue (from embryos with crown-rump length (CRL) 13-16 mm) was transplanted into adult and aged isogenetic mice to study the growth of serotonergic fibers between host and donor tissue. A specific antibody against serotonin (5-HT) was used to immunocytochemically visualize 5-HT containing cell bodies and fibers. Unilateral fetal transplants into the hippocampi of adult (4-6 mo.) or aged (24 mo.) mice matured and sent out processes which very densely innervated the transplant tissue itself and extended into the host hippocampus. The termination of these fibers was consistent with the known 5-HT-hippocampal lamination pattern in normal animals. Qualitative comparisons suggested that the density of outgrowth into adult hippocampus was greater than into aged hippocampus. Conversely, adult 5-HT neurons send sprouts into fetal hippocampal tissue transplanted into the lateral ventricle. Therefore, immunocytochemical procedures can be used to monitor outgrowth from the fetal tissue to the host and ingrowth from the adult host to the fetal tissue. Furthermore, the apparent normal 5-HT lamination pattern produced by fetal raphe axons in adult hippocampus is consistent with reports that neuronal transplantation is effective in reversing the anatomical and behavioral deficits produced by homotypic denervation of a terminal field.

Age Factors↗