Fine structure of a lepidopteran nervous system and its accessibility to peroxidase and lanthanum

Summary The avascular ventral nerve cord of the moth, Manduca sexta, possesses an extensive dorsal mass of connective tissue in which lie fibroblasts that produce a collagen-like protein. The lateral and ventral surfaces of the nerve cord are ensheathed by an acellular neural lamella. Beneath this lies a layer of microtubule-laden perineurial cells which are separated from one another at their peripheral borders by lacunae containing electron-opaque material to which the cells are attached by hemi-desmosomes. Beyond these spaces, narrow intercellular clefts occur between the interdigitating perineurial plasma membranes; these are then connected by both gap and tight junctions. The axons beneath are surrounded by glia which also contain many microtubules and which are linked to one another by desmosomes and tight junctions.When intact nerve cords are incubated in horseradish peroxidase, reaction product is subsequently found within the neural lamella as well as in the lacunae and clefts between perineurial cells, but not beyond this level. Desheathed preparations, however, contain peroxidase within the cytoplasm of the exposed glial cells. Lanthanum penetrates the neural lamella and the lacunae, clefts and gap junctions between adjacent perineurial cells, but no further. It therefore appears that the tight junctions in the perineurium may be the site of restriction to the entry of ions and molecules, the existence of which has been suggested previously by electrophysiological investigations.I am grateful to Miss Yvonne R. Carter for her invaluable technical assistance and to Dr. J.E. Treherne and Dr. D.B. Sattelle for helpful discussions.     

The role of neurotrophins in the developing nervous system

Neurotrophins were originally identified by their ability to promote the survival of developing neurons. However, recent work on these proteins indicates that they may also influence the proliferation and differentiation of neuron progenitor cells and regular several differentiated traits of neurons throughout life. Moreover, the effects of neurotrophins on survival have turned out to be more complex than originally thought. Some neurons switch their survival requirements from one set of neurotrophins to another during development, and several neurotrophins may be involved in regulating the survival of a population of neurons at any one time. Much of our understanding of the developmental physiology of neurotrophins has come from studying neurons of the peripheral nervous system. Because these neurons and their progenitors are segregated into anatomically discrete sites, it has been possible to obtain these cell for in vitro experimental studies from the earliest stage of their development. The recent generation of mice having null mutations in the neurotrophin and neurotrophin receptor genes has opened up an unparalleled opportunity to assess the physiological relevance of the wealth of data obtained from these in vitro studies. Here I provide a chronological account of the effects of members of the NGF family of neurotrophins on cells of the neural lineage with special reference to the peripheral nervous system. 1994 John Wiley & Sons, Inc.     

Insect peripheral nerves: accessibility of neurohaemal regions to lanthanum.

During incubation in vivo, exogenously applied ionic lanthanum comes to surround the numerous neurosecretory terminals which are found lying within or immediately beneath the acellular neural lamella ensheathing the nerves from fifth instar and adult specimens of Rhodnius prolixus. The lanthanum does not penetrate beyond the cellular perineurium, which completely surrounds the non-neurosecretory axons in these nerves and constitutes a form of 'blood-brain barrier'. In some cases, however, lanthanum is found in the vicinity of a neurosecretory axon lying beneath the perineurium, where it can be assumed to have leaked in from the neurosecretory terminal lying free in the neural lamella. When nerves are incubated in calcium-free media, regions with an attenuated perineurium become 'leaky', in that lanthanum is found lying in those extracellular spaces between axons and glia which lie immediately below the thin part of the perineurial layer. Bathing solutions made slightly hyperosmotic to the haemolymph with sucrose have no apparent disruptive effects on the barrier. When the tissues are incubated in more hypertonic solutions, the perineurial barrier becomes 'leaky' throughout, and tracer pervades beyond its cells into all the intercellular spaced between glia and axons. The possible role of the zonulae occludentes in both the maintenance of the perineurial barrier and in the formation of interglial occlusions to local penetration of exogenous substances is considered.     

Cell death and the developing enteric nervous system

This review discusses current knowledge about cell death in the developing enteric nervous system (ENS). It also includes findings about the molecular mechanisms by which such death is mediated. Additional consideration is given to trophic factors that contribute to survival of the precursors and neurons and glia of the ENS, as well to genes that, when mutated or deleted, trigger their death. Although further confirmation is needed, present observations support the view that enteric neural crest-derived precursor cells en route to the gut undergo substantial levels of apoptotic death, but that once these cells colonize the gut, there is relatively little death of precursor cells or of neurons and glia during the fetal period. There are also indications that normal neuron loss occurs in the ENS, but at times beyond the perinatal stage. Taken together, these findings suggest that ENS development is similar is some ways, but different in others from extra-enteric areas of the vertebrate central and peripheral nervous systems, in which large-scale apoptotic death of precursor neurons and glia occurs during the fetal and perinatal periods. Potential reasons for these differences are discussed such as a fetal enteric microenvironment that is especially rich in trophic support. In addition to the cell death that occurs during normal ENS development, this review discusses mechanisms of experimentally-induced ENS cell death, such as those that are associated with defective glial cell-line derived neurotrophic factor/Ret signaling, which are an animal model of human congenital megacolon (aganglionosis; Hirschsprung’s disease). Such considerations underscore the importance of understanding cell death in the developing ENS, not just from a curiosity-driven point of view, but also because the pathophysiology behind many disorders of human gastrointestinal function may originate in abnormalities of the mechanisms that govern cell survival and death during ENS development.     

The human immunodeficiency virus type 1 and the developing central nervous system

Currently, at least 42 million people are infected worldwide with the human immunodeficiency virus type 1 (HIV-1). Of these, 3.2 million are children infected, in 90% of the cases, through vertical transmission. In Colombia, approximately 200,000 persons have been infected since the beginning of the pandemic, with an increasing trend in the seroprevalence among pregnant women. Although HIV-1 is basically lymphotropic, its capacity to invade the central nervous system (CNS) is well known, generating multiple neurological alterations, especially prominent in children, with encephalopathy being the most prevalent. Classically, two types of neurological disorders are recognized in children, consisting of early and late encephalopathies, each with differing clinical and immunological characteristics. HIV-1 infection of the CNS is limited to macrophages, microglia and astrocytes in a restricted manner. In patients with acquired immunodeficiency virus (AIDS), neurons are rarely infected, suggesting that cellular and viral soluble factors, are responsible for the neuronal damage. The conclusion is that the CNS in earlier stages of development is especially susceptible to HIV-1 infection. The epidemiological trends predict that these types of clinical manifestations of HIV-1 will increase in frequency, and increases the necessity for an understanding of the underlying neuropathogenesis.     

Neural activity and survival in the developing nervous system

Recent evidence suggests that blockade of normal excitation in the immature nervous system may have profound effects on neuronal survival during the period of natural cell death. Cell loss following depression of electrical activity in the central nervous system (CNS) may explain the neuropsychiatric deficits in humans exposed to alcohol or other CNS depressants during development. Thus, understanding the role of electrical activity in the survival of young neurons is an important goal of modern basic and clinical neuroscience. Here we review the evidence from in vivo and in vitro model systems that electrical activity participates in promoting neuronal survival. We discuss the potential role of moderate elevations of intracellular calcium in promoting survival, and we address the possible ways in which activity and conventional trophic factors may interact.     

The penetration of ionic lanthanum into the central nervous system of the tick, Amblyomma variegatum

ABSTRACT. The ultrastructure of the tick central nervous system resembles that of insects except that the perineurial layer of specialized glial cells is less well developed in the tick. In particular, the cells are not connected by tight or septate junctions. Probably as a consequence, ionic lanthanum penetrates the entire central nervous system of the tick, whereas it fails to penetrate the perineurium of insects. These observations suggest that ticks lack the 'blood—brain barrier' which protects the insect nervous system.     

Biochemical changes in the developing rat central nervous system due to hyperthermia

Rat embryos at 10 days of gestation were exposed to 43 degrees C for 8 minutes by submerging the exteriorized right uterine horn in heated saline solution and then reinserting the uterine horn into the abdominal cavity. At 15 days, the fetuses were removed, and cells from the cerebral hemispheres were dissociated and grown as primary cultures. Embryos from the left uterine horn served as controls. No morphological changes were observed between the cultures of cells from control and heat-exposed embryos at different days in culture. However, exposure of embryos to hyperthermia at 10 days significantly affected the developmental pattern of activities of acetylcholine esterase associated with cholinergic neurons and of 2',3'-cyclic nucleotide phosphohydrolase associated with oligodendrocytes and myelin membrane formation. These results suggest that hyperthermia at 10 days of gestation in the rat may lead to an impairment in the development of neurons and oligodendrocytes in the central nervous system.     

The origin of spontaneous activity in developing networks of the vertebrate nervous system

Spontaneous neuronal activity has been detected in many parts of the developing vertebrate nervous system. Recent studies suggest that this activity depends on properties that are probably shared by all developing networks. Of particular importance is the high excitability of recurrently connected, developing networks and the presence of activity-induced transient depression of network excitability. In the spinal cord, it has been proposed that the interaction of these properties gives rise to spontaneous, periodic activity.