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Biomedical subjects

J M Lauder

Publications and source records attributed to J M Lauder.

At least 109 records · Page 6Linked to original sources
PubMed1981

Maternal influences on tryptophan hydroxylase activity in embryonic rat brain.

Maternal treatment with p-chlorophenylalanine strongly inhibits brain tryptophan hydroxylase (TPH) activity in the embryo, whereas administration of tryptophan significantly elevates the activity of this enzyme. Maternal stress, glucocorticoid injections, or a corn diet (low in tryptophan) do not change embryonic TPH activity, however. Since TPH is thought to be rate-limiting for serotonin (5-HT) synthesis in the developing animal as well as in the adult altered TPH activity as a result of maternal influences could change 5-HT synthesis in the embryo. If 5-HT is a developmental signal in the early differentiation of specific neurons during embryogenesis, as previously suggested, such maternal influences could affect this process, resulting in altered neuronal genesis in those brain regions receiving a serotonergic innervation.

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PubMed1980

Cerebellar granule cell genesis in the hydrocortisone-treated rats.

The development of the cerebellar cortex was studied by quantitative light microscopic methods in rats treated with hydrocortisone on postnatal days 7-18. This treatment resulted in a decreased number of cells in the external granular layer (EGL) and an early disappearance of the EGL. In the adult cerebellum of these neonatally treated animals, the total number of granule cells in lobule VIII was decreased by 41% and that of molecular layer microneurons by 28%. Autoradiographic determinations of the 'birthdays' (time of origin) of cerebellar microneurons showed that the peaks of cell formation in the internal granular and molecular layers occurred at earlier ages than in controls. In the granule cell population, this observation was the result of both decreased cell proliferation during the treatment and premature cessation of division in granule cell precursors in the EGL. The morphological effects of 'late' hydrocortisone treatment on the cerebellum observed in this study are compared with those of 'early' hydrocortisone treatment on days 1-4 and those of thyroid hormone from previous studies. It is suggested that endogenous levels of both thyroid and glucocorticoid hormones during the neonatal period may influence the rate of neurogenesis in the postnatal rat cerebellum.

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PubMed1978

Serotonin as a differentiation signal in early neurogenesis.

The hypothesis that serotonin (5-HT) influences the onset of differentiation (cessation of division) of prospective 5-HT target neurons during embryogenesis was tested by administering the 5-HT depleting drug p-chlorophenylalanine (pCPA) to pregnant rats and dating the time of last cell division for fetal neurons using long survival 3H-thymidine autoradiography. PCPA specifically retarded the onset of neuronal differentiation in brain regions known to contain 5-HT terminals or to have a high 5-HT content in the adult (5-HT target cells). Conversely, the 'stress' of daily vehicle injections accelerated onset of differentiation in these regions, possibly due to stimulation of 5-HT synthesis by glucocorticoids. These data support the model of 5-HT as a humoral signal for the differentiation of cells later recognized by 5-HT neurons as appropriate targets for synaptogenesis.

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PubMed1977

The effects of early hypo- and hyperthyroidism on the development of rat cerebellar cortex. III. Kinetics of cell proliferation in the external granular layer.

The effects of early hypo- and hyperthyroidism on the rates of cell acquisition and proliferation have been studied in the external granular layer (EGL) of the developing rat cerebellar cortex at 10 days of age using quantitative autoradiographic methods. Both altered thyroid states reduce the rate of cell acquisition in the EGL, but appear to do so for different reasons. Hyperthyroidism shortens the average length of the cell cycle by decreasing the duration of the pre-DNA synthetic phase (G1), indicating that excess thyroxine may exert a direct effect on the EGL. This action involves the early onset of neuronal differentiation (cessation of proliferation)46 which presumably leads to the observed decrease in the rate of cell acquisition (increased doubling time). Such differentiating cells do not, however, leave the proliferative zone or the EGL prematurely, resulting in a reduced labeling index, mitotic index, and growth fraction as non-dividing cells dilute the proliferating cell population. Hypothyroidism, on the other hand, leads to no significant change in the length of the cell cycle or in the mitotic index, but causes a decreased labeling index and growth fraction, as well as a reduced rate of cell acquisition (increased doubling time). No significant change in the amount of cell death in the EGL could be found to explain this apparent discrepancy between the rate of cell proliferation (cell cycle length) and cell acqusiition. The answer to this puzzle appears to lie in the mitotic index, which is not affected to the same extent as the labeling index, although it is also slightly reduced. If cells were to remain longer in mitosis, this could result in a decreased labeling index and growth fraction but nearly normal mitotic index and cell cycle length (as measured using the % labeled mitoses method), since those cells dropping out of the cycling population would be counted as mitoses...

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PubMed1975

Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. II. Synaptogenesis.

Synaptogenesis was studied in the monoamine (MA) cell groups locus coeruleus (LC), dorsal and medial raphe nuclei (RN) and substantia nigra, zona compacta (SN) between day 18 of gestation and postnatal day 60 using ethanolic phosphotungstic acid (E-PTA) to visualize synaptic profiles. Nuclear area, and cellular packing density (inversely proportional to area of neuropil) were also determined. As determined using the E-PTA method, synaptogenesis begins in the neuropil of the SN first, on or before 18 days of gestation, and in the LC and RN at 19 days. Synaptogenesis on MA cell perikarya is first observed in the SN, on or before 18 days, and in the LC and RN at 20 days. The onset of somatic synaptogenesis coincides with the beginning of nuclear growth and development of the neuropil (decrease in cellular packing density) in all MA cell areas, raising the possibility of common factors in the initiation of these processes. Nonsynaptic contacts precede the appearance of synaptic profiles both in the neuropil and on the somata of the MA cells of the LC, RN and SN, and may represent precursors of mature synapses or desmosome-like contacts. Somatosomatic nonsynaptic contacts occur only prenatally between adjacent MA neurons in the LC, RN and SN. Although some synaptogenesis occurs prenatally in these MA cell groups (indiciating that these parts of the MA circuitry may be functional before birth), most of this synaptogenesis occurs postnatally and continues into adulthood. Since such synaptogenesis does not begin until 2-4 days prior to birth, whereas these neurons and their processes exhibit MA fluorescence as early as 12-14 days of gestation, they apparently are capable of synthesizing transmitter and proliferating terminals before they themselves are innervated.

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PubMedDate not supplied

Simple method for the culture of glial cells from embryonic rat brain: implications for regional heterogeneity and the radial glial lineage.

A simple method is described for the production of glial cell cultures from specific regions of the day 13-15 embryonic rat brainstem and midbrain based on differential cell attachment to a relatively nonadhesive substrate, which inhibits the growth of neurons. Regional differences in the ability of specific populations of brainstem and midbrain cells to attach and spread on the substrate suggest that embryonic glial populations may differ in their cell surface properties even when they derive from the same general area of the developing brain. Based on observations of the spatiotemporal distribution of radial-like glial cells and astrocytes with time in vitro, we suggest that this culture system may prove useful for investigation of the radial glial lineage.

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PubMedDate not supplied

Changes in the physiological roles of neurotransmitters during individual development.

The classical neurotransmitters (acetylcholine and biogenic monoamines) are multifunctional substances involved in intra- and intercellular signaling at all stages of ontogenesis in multicellular animals. A cyclical scheme is proposed to describe age-related changes in neurotransmitter functions at different stages of development from oocyte maturation to neuron formation. This may reflect not only the temporospatial organization of neurotransmitter processes, but also the origin of the functions of acetylcholine and biogenic monoamines from the protosynapses of the cleaved embryo to neuronal synapses.

Aging↗
PubMedDate not supplied

Serotonin immunocytochemistry in the adult and developing rat brain: methodological and pharmacological considerations.

An antiserum has been raised in rabbits against serotonin (5-HT) conjugated to the invertebrate protein hemocyanin (HC). This antiserum was characterized with respect to its cross-reactivity with related compounds and its immunocytochemical staining properties in brains of adult and developing rats and in animals pretreated with various pharmacological regimens. When compared to an antiserum raised against 5-HT/bovine serum albumin (BSA) conjugates [59], the 5-HT/HC conjugate elicited a more profound immune response which resulted in the production of a specific, high titer antiserum that could be used directly for immunocytochemistry without removal of antibodies to the invertebrate carrier molecule, HC. Immunoabsorption experiments to assess the specificity of this antiserum demonstrated a small degree of cross-reactivity with dopamine (which was greater than that with norepinephrine or epinephrine). However, no staining of catecholaminergic neurons was found in untreated adult or developing animals, nor in animals pretreated with L-DOPA or L-DOPA + the MAO inhibitor nialamide, indicating that this cross-reactivity is not manifested under normal staining conditions. No cross-reactivity of the 5-HT/HC antiserum was observed for any 5-HT precursors or metabolites tested, although both this antiserum and the 5-HT/BSA antiserum did exhibit a high degree of cross-reactivity to the related indoleamines 5-methoxytryptamine (5-MT) and tryptamine. However, based on the immunocytochemical staining patterns observed, and the fact that both 5-MT and tryptamine are found in very low quantities in the normal rat brain, it appears that 5-HT is the predominant indoleamine stained by both of these antisera in the untreated rat brain. In animals pretreated with L-tryptophan + nialamide, some light staining was found in the dopaminergic A9 and A10 cell groups using either antiserum. However, since this staining was not observed in L-DOPA + nialamide treated animals it is not thought to be due to cross-reactivity with dopamine. Rather, since the staining could be inhibited by pretreatment with the catecholaminergic uptake blocker desmethylimipramine, it is postulated that this effect may be due to either (1) the non-specific uptake of 5-HT or 5-hydroxytryptophan (5-HTP) into the dopaminergic cells of A9 and A10 due to elevated levels of these substances in the dense serotonergic axonal plexus passing through this region or (2) to an increased uptake of circulating L-tryptophan by these A9 and A10 cells followed by conversion of this amino acid to tryptamine by aromatic amine decarboxylase, an enzyme common to both 5-HT and dopaminergic neurons. This latter possibility suggests that caution should be exercised when interpreting immunocytochemical staining patterns obtained in animals pretreated with L-tryptophan + nialamide using 5-HT antisera, since other cross-reactive indoleamines could be elevated by this pharmacological manipulation.

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PubMedDate not supplied

In vivo and in vitro development of serotonergic neurons.

The monoamines are one of the earliest developing neurotransmitter systems in the mammalian brain. The first part of this paper describes the normal ontogeny of the serotonergic (5-HT) system in the rat brain as studied using long survival 3H-thymidine autoradiography (time of neuronal genesis, time of origin) and the Falck-Hillarp histofluorescence method, electron microscopy, and immunocytochemistry (anti-5-HT). Due to their early ontogeny relative to other brain regions, 5-HT neurons (as well as monoamine neurons in general) have been suggested to exert some type of "trophic" influence on brain development. Results of pharmacological experiments designed to inhibit 5-HT synthesis in the embryonic rat brain by maternal treatment with p-chlorophenylalanine (pCPA) at a time when this monoamine might exert such an influence are discussed with regard to effects on the time course of neuronal genesis (time of origin) of 5-HT neurons and their target cells. These results, which prompted us to propose that 5-HT might act as a "differentiation signal" for certain of its target cells, are now discussed in light of our more recent immunocytochemical-autoradiographic studies (anti-5-HT, 3H-thymidine) which morphologically demonstrate close associations between developing 5-HT neurons and proliferating neuroepithelial cells in the embryonic brain. Postnatal studies using this immunocytochemical-autoradiographic method also provide evidence for interactions of 5-HT axons with proliferating glioblasts in the developing cerebellum and with immature granule cells and their precursors in the hippocampus. These findings, in conjunction with the results of our pCPA experiments, further enhance the possibility that 5-HT neurons could exert an epigenetic influence on the development of less differentiated cells with which they come into contact. Finally, preliminary studies using dissociated cell cultures containing 5-HT neurons suggest that interactions between 5-HT neurons and glial elements may be important for the differentiation of these neurons in vitro. Whether 5-HT neurons in turn influence the development of glial or neuronal cells in these cultures remains to be determined. These studies are evaluated with regard to a possible pre-transmission role for 5-HT during key phases of neuronal and glial genesis.

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PubMedDate not supplied

Serotonin uptake in the ectoplacental cone and placenta of the mouse.

The neurotransmitter serotonin (5-HT) was localized in the ectoplacental cone (EPC) and placenta of the day 9-12 (E9-12) mouse embryo in vivo and in whole embryo cultures, using immunocytochemistry with a specific 5-HT antiserum. In uncultured conceptuses, 5-HT immunoreactivity (5-HT IR) was most intense in the EPC at E9 (2-7 somites), particularly in giant cells around the periphery. Nuclear staining was observed in lightly staining giant cells and in small cells in the core of the cone. By E10 (18-24 somites) 5-HT IR in the placenta was less intense and almost exclusively limited to giant cells, where it was localized to chromatin-like material in nuclei. The same pattern and level of 5-HT IR persisted through E12. In the placenta, 5-HT IR appeared to be most intense in giant cells located near aggregations of platelets in decidual blood vessels. 5-HT IR was enhanced in cultured conceptuses, and further increased when exogenous 5-HT was added to the culture medium. Immunoreactivity was greatly reduced by adding the 5-HT uptake inhibitor fluoxetine to the culture medium, or culturing conceptuses in medium containing 5-HT depleted rat serum. Thus, 5-HT was apparently taken up from the culture medium. In conceptuses exposed to exogenous 5-HT, immunoreactivity in the placenta appeared as a gradient from the giant cells to the inner layers, suggesting that these cells may transport 5-HT toward the embryo. No evidence of 5-HT synthesis by the EPC/placenta was found. These results suggest that 5-HT present in the EPC/placenta is due to uptake, not synthesis. Possible sources and functions of 5-HT in the developing placenta are discussed.

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