Search PubMed⌕ Search

Biomedical subjects

P Levitt

Publications and source records attributed to P Levitt.

120 records · Page 7Linked to original sources
PubMed1978

Developmental organization of raphe serotonin neuron groups in the rat.

The pre- and early postnatal development of serotonin neurons in the rat brainstem was studied using the fluorescence histochemical method. The technique utilized does not require drug pretreatment to visualize an intense serotonin fluorophore localized in neuronal perikarya, dendrites, and axons. All the serotonin neuron groups develop as bilateral nuclei which extend from the midbrain through the medulla. Six of the nine groups undergo a midline fusion from embryonic day 18 (E 18) through postnatal day 6 (P 6) in a rostrocaudal gradient. Cells of the nucleus raphe dorsalis fuse first (by P 1), whereas the serotonin neurons located in nucleus raphe pallidus do not fuse until P 6. This gradient is comparable to the one described for the first observable fluorescence in the serotonin neurons groups. After final cell division, the serotonin neurons undergo a primary migration from the ventricular zone along the midline, where they are situated during embryogenesis, and a secondary migration extending into postnatal life which concludes with fusion in the midline. The bilateral origins of the serotonin cell groups are maintained in the adult. This is expressed by the apparent ipsilateral projections of some of the raphe neurons determined recently in our laboratory utilizing autoradiographic and horseradish peroxidase techniques.

Animals↗
PubMed1978

Noradrenaline neuron innervation of the neocortex in the rat.

Noradrenaline innervation of the rat neocortex is studied by glyoxylic acid histochemistry and radioisotopic biochemical analysis. The data indicate that all neocortical areas receive a noradrenergic innervation which is identical in organization but varies in density from area to area. Radioisotopic analysis of catecholamines in the cortical areas studied reveals only the presence of significant levels of noradrenaline. Unilateral locus coerulus ablation greatly diminishes ipsilateral noradrenaline content and fiber innervation in all neocortical areas studied. Detailed histochemical analysis reveals a diffuse plexus-like arrangement of noradrenaline fibers, with each cortical layer having a distinctive pattern of innervation. Single noradrenergic fibers enter layer VI of cortex and branch at all levels to undergo extensive collateralization. Terminal horizontal branching in the molecular layer results in the most dense fiber plexus of all cortical layers. This pattern of noradrenaline innervation is similar to that of other non-specific afferent systems innervating neocortex.

Animals↗
PubMed1976

Selective cell association of catecholamine neurons in brain aggregates in vitro.

Brain tissues (aggregates) were reconstructed in vitro from dissociated single cell suspensions derived from 12- to 18-day embryonic mouse midbrain containing the substantia nigra. The application of the Falck-Hillarp histofluorescence method to these cell systems allows the visualization and identification of this specific population of developing catecholamine (CA) neurons during their reassembly, differentiation and histogenetic patterning in vitro. CA neurons are unselectively distributed in the initial dissociated cell suspension and in the reaggregating tissue up to 24 h. By 48 h the CA neurons have selectively associated into small clusters which further coalesce into a thick and elongated band along one margin of the aggregate by 96 h. This structure is similar in organization to the morphology exhibited by substantia nigra neurons in situ during their migratory phase in normal development. In addition, the differentiated neurons observed in the later aggregates appear to produce normal processes. Catecholamine analyses show a significant increase in dopamine and noradrenaline levels during the process of differentiation and histogenetic organization in vitro.

Animals↗
PubMed1976

Disseminated histoplasmosis and necrotizing vasculitis.

A 74-year-old man with congestive heart failure was found to have Histoplasma capsulatum in a lesion of the right nasal septum. His initial treatment with amphotericin B was inadequate because of severe intolerance to the drug. Three months after initial presentation H. capsulatum was detected in his blood and bone marrow. Slightly elevated purpuric lesions on the arms, lower legs and trunk showed the typical features of necrotizing vasculitis. Cutaneous anergy was reversed after treatment with transfer factor. Skin involvement in disseminated histoplasmosis is unusual and there are no previous reports of vasculitis associated with this infection.

Aged↗
PubMedDate not supplied

The critical impact of early cellular environment on neuronal development.

Normal brain development requires the precise interactions of environmental signals with genes that drive cellular differentiation and circuit formation. Experimental studies in animal models reveal that early environmental influences in utero can modulate cell fate choice and neuronal growth. Modification of the determinants can have long-lasting consequences. Studies using transplant and cell culture methods have examined the development of the limbic system, regions of the brain that mediate cognition, emotion, memory, and learning. The results show that growth factors in the environment of progenitor cells control long-term gene expression that characterizes neurons in limbic brain regions. Other studies in which the cellular environment is altered by prenatal cocaine exposure result in modified fetal neurotransmitter function and specific pharmacological and structural alterations in the cerebral cortex that lead to abnormal behavior. The cellular milieu of the developing central nervous system prenatally thus serves functions as critical as environmental stimuli postnatally that promote synaptic development and refinement.

Animals↗
PubMedDate not supplied

Prenatal effects of drugs of abuse on brain development.

Drugs of abuse modify signaling of neurotransmitter systems and intracellular messengers. Recent studies of central nervous system development show that these same neurotransmitters may serve as molecules that regulate specific aspects of cell proliferation, survival, migration, circuit formation and establishment of topography. Moreover, the convergence of neurotransmitter, growth factor and hormone activity on similar intracellular signaling systems suggests the potential for significant interactions among molecular components that regulate development. The application of modern strategies used by developmental and cell biologists to the question of whether prenatal drug exposure alters brain structure and function has led to discoveries of specific, targeted changes. Studies of the mechanisms of drug action that lead to altered neural development are now reality.

Animals↗
PubMedDate not supplied

Cerebral cortical progenitors are fated to produce region-specific neuronal populations.

The mammalian cerebral cortex is characterized by its organization into anatomically and functionally discrete regions. During cortical development, a homogeneous-appearing population of cells along the ventricular surface generates the neurons and glia that ultimately form these cytoarchitectonic areas. The limbic system-associated membrane protein (LAMP) is a neuronal, cell surface glycoprotein that identifies neurons restricted to limbic cerebral cortical areas (Levitt, 1984). LAMP is expressed early in development (Horton and Levitt, 1988), and transplantation studies in the rat suggest that cells in the cerebral wall are committed to a limbic or nonlimbic molecular phenotype by embryonic day 14 (E14) (Barbe and Levitt, 1991). However, at E12, cells destined for the cerebral cortex are still multipotential and presumably depend on local, extrinsic signals to adopt a limbic phenotype. We have developed an in vitro assay system for examining the fate of these multipotential progenitors and identifying potential environmental regulators of neuronal differentiation. Regions of the lateral (limbic) and dorsal (nonlimbic) cerebral wall at E12 are dissected, dissociated, and grown in low-density cultures in defined medium. The cells are examined by immunocytochemistry for expression of MAP2, a neuronal cytoskeletal protein, and LAMP to define neuronal differentiation and the expression of a limbic molecular phenotype, respectively. We find that after 4 d in culture, up to 75% of the progenitor cells from presumptive limbic cortex express LAMP upon differentiation. In contrast, only 20-30% of the differentiated cells from presumptive sensorimotor cortex express LAMP. Thus, most cortical progenitors are fated to a limbic or nonlimbic phenotype early in development, and the decision by neuronal stem cells to differentiate into neurons exhibiting this molecular phenotype occurs prior to the completion of neurogenesis, in the absence of subcortical environmental cues.

Animals↗
PubMedDate not supplied

Nonuniform alteration of dendritic development in the cerebral cortex following prenatal cocaine exposure.

Prenatal exposure to cocaine has the potential to modify normal brain development and result in behavioral dysfunction. We used a new animal model in which cocaine was administered intravenously during prenatal development in pregnant rabbits twice daily at low dosages. Analysis of brain development focused on two areas of the cerebral cortex, anterior cingulate and primary visual, in which dopamine afferents, a target of cocaine, are differentially distributed. All postnatal rabbits exposed to cocaine prenatally exhibited normal features of cortical organization, including thickness, lamination patterns, and cytoarchitectonic differentiation. General axonal and astroglial organization, assessed by neurofilament-H and glial fibrillary acidic protein immunostaining, also was unchanged in the cocaine-exposed animals. Analysis of dendritic organization was done using antibodies against microtubule-associated protein 2 (MAP2), which reveals mostly the larger apical shafts of cortical pyramidal cells. In the anterior cingulate cortex of adolescent rabbits exposed to cocaine in utero, there is a marked decrease in both dendritic bundling and typical long, straight MAP2-stained profiles. In normal animals, the long, bundled dendrites area readily traced in a single focal plane from layer III or V pyramidal cell somata to the pial surface in saline-treated animals. Instead, the drug-exposed animals contained many more short segments of MAP2-stained dendrites that could be viewed coursing in and out of the plane of focus in the sections. Apical dendrites in mature visual cortex appeared normal in the cocaine-exposed rabbits. Examination of MAP2 staining at various postnatal ages revealed that the dendritic changes expressed in the adolescent anterior cingulate cortex appeared less robust, but still evident at birth. By P10-14, dendritic modifications were similar to the adult. Counts of the number of MAP2-positive dendritic profiles crossing the layer II-III interface reached a nadir of 50% in the cocaine-exposed animals, indicative of a change in the organization of the apical dendrites compared to the control animals. Dendritic profiles of anterior cingulate neurons, filled by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholate (Dil), confirmed that in the cocaine offspring, the dendrites coursed in an irregular, wavy manner from deep to superficial layers, suggestive of dendrites that were longer than normal, although cortical thickness was unchanged. The altered dendritic profiles also were seen in Golgi-impregnated neurons. The data indicate that prenatal exposure to cocaine can lead to specific alterations of neuronal growth that are long lasting. The lack of dendritic changes in visual cortex suggests that the drug does not modify development of cortical regions uniformly. This study also provides a new focus on the anterior cingulate cortex as a site in which aberrant structure-function relationships following prenatal cocaine exposure should be examined in both animal models and clinically.

Animals↗
PubMedDate not supplied

Complementary distribution of collagen type IV and the epidermal growth factor receptor in the rat embryonic telencephalon.

We previously identified an interaction between collagen type IV and the EGF receptor that regulates the differentiation of a limbic cortical phenotype in vitro (Ferri and Levitt, 1995). In the present study, we map the expression of the EGF receptor and collagen type IV in the embryonic telencephalon of the rat. At embryonic day (E) II, the earliest age examined, both proteins are coexpressed throughout the ventricular zone in the cerebral wall; this zone remains immunoreactive throughout corticogenesis (E14-E19). The cells comprising the subventricular zone are the most intensely immunoreactive for the EGF receptor, although little collage type IV is detected in this region. In contrast, postmitotic neurons that leave the proliferative zones are negative for the receptor. Moreover, during the peak of neuronal migration, the intermediate zone lacks collagen type IV immunoreactivity. Neurons that settle in the cortical plate once again exhibit EGF receptor immunoreactivity; this same zone is devoid of collagen type IV. By E19, coexpression of both proteins is evident only in the rostral extension of the subventricular zone, the pathway of migrating cells leading to the olfactory bulb. The temporal and spatial overlap of the EGF receptor and collage type IV in the cortical progenitor pool in vivo indicates that these molecules may participate in the initial decisions of neuronal differentiation. Their modified distribution during cortical maturation suggests a changing role for both proteins.

Animals↗