A Combination of PLP and DM20 Transgenes Promotes Partial Myelination in the Jimpy Mouse

Abstract: Mutations in the myelin proteolipid protein (PLP) gene, such as that found in the jimpy mouse, result in an abnormal structure of the myelin, severe dysmyelination, and a reduction in the number of mature oligodendrocytes. To examine the functions of the two alternatively spliced isoforms of proteolipid protein, transgenic mice were generated that express either PLP or DM20 cDNAs placed under control of the PLP upstream regulatory region. The transgenes were bred into jimpy mice, and the effect of the transgenes on the dysmyelinating phenotype was analyzed. Neither the PLP transgene nor the DM20 transgene alone had an effect on myelination in the jimpy mice. Combining the two transgenes substantially increased the number of myelinated axons, suggesting that the two alternatively spliced products of the PLP locus perform distinct functions in oligodendrocytes. The enhanced myelination was not sufficient, however, for completely correcting the dysmyelinating phenotype of the jimpy mice, nor was it accompanied by the restoration of normal levels of myelin gene expression. The inability to rescue the jimpy phenotype is most likely attributable to a dominant negative action of the abnormal proteolipid proteins present in jimpy mice. These results demonstrate the complexity of proteolipid protein function in myelination.     

The Role of the Oligodendrocyte Lineage in Acute Brain Trauma

An acute brain injury is commonly characterized by an extended cellular damage. The post-injury process of scar formation is largely determined by responses of various local glial cells and blood-derived immune cells. The role of astrocytes and microglia have been frequently reviewed in the traumatic sequelae. Here, we summarize the diverse contributions of oligodendrocytes (OLs) and their precursor cells (OPCs) in acute injuries. OLs at the lesion site are highly sensitive to a damaging insult, provoked by Ca²⁺ overload after hyperexcitation originating from increased levels of transmitters. At the lesion site, differentiating OPCs can replace injured oligodendrocytes to guarantee proper myelination that is instrumental for healthy brain function. In contrast to finally differentiated and non-dividing OLs, OPCs are the most proliferative cells of the brain and their proliferation rate even increases after injury. There exist even evidence that OPCs might also generate some type of astrocyte beside OLs. Thereby, OPCs can contribute to the generation and maintenance of the glial scar. In the future, detailed knowledge of the molecular cues that help to prevent injury-evoked glial cell death and that control differentiation and myelination of the oligodendroglial lineage will be pivotal in developing novel therapeutic approaches.     

Dystroglycan promotes filopodial formation and process branching in differentiating oligodendroglia

During central nervous system (CNS) development, individual oligodendrocytes myelinate multiple axons, thus requiring the outgrowth and extensive branching of oligodendroglial processes. Laminin (Lm)-deficient mice have a lower percentage of myelinated axons, which may indicate a defect in the ability to properly extend and branch processes. It remains unclear, however, to what extent extracellular matrix (ECM) receptors contribute to oligodendroglial process remodeling itself. In the current study, we report that the ECM receptor dystroglycan is necessary for Lm enhancement of filopodial formation, process outgrowth, and process branching in differentiating oligodendroglia. During early oligodendroglial differentiation, the disruption of dystroglycan-Lm interactions, via blocking antibodies or dystroglycan small interfering RNA (siRNA), resulted in decreased filopodial number and length, decreased process length, and decreased numbers of primary and secondary processes. Later in oligodendrocyte differentiation, dystroglycan-deficient cells developed fewer branches, thus producing less complex networks of processes as determined by Sholl analysis. In newly differentiating oligodendroglia, dystroglycan was localized in filopodial tips, whereas, in more mature oligodendrocytes, dystroglycan was enriched in focal adhesion kinase (FAK)-positive focal adhesion structures. These results suggest that dystroglycan-Lm interactions influence oligodendroglial process dynamics and therefore may regulate the myelination capacity of individual oligodendroglia.     

Astrocyte,the star <Emphasis Type="Italic">avatar</Emphasis>: redefined

Until recently, the neuroscience community held the belief that glial cells such as astrocytes and oligodendrocytes functioned solely as “support” cells of the brain. In this role, glial cells simply provide physical support and housekeeping functions for the more important cells of the brain, the neurons. However, this view has changed radically in recent years with the discovery of previously unrecognized and surprising functions for this underappreciated cell type. In the past decade or so, emerging evidence has provided new insights into novel glial cell activities such as control of synapse formation and function, communication, cerebrovascular tone regulation, immune regulation and adult neurogenesis. Such advances in knowledge have effectively elevated the role of the astrocyte to one that is more important than previously realized. This review summarizes the past and present knowledge of glial cell functions that has evolved over the years, and has resulted in a new appreciation of astrocytes and their value in studying the neurobiology of human brain cells and their functions. In this review, we highlight recent advances in the role of glial cells in physiology, pathophysiology and, most importantly, in adult neurogenesis and “stemness”, with special emphasis on astrocytes.     

Social relations between adult males and females of Japanese monkeys in the arashiyama B troop

Some dyads of Japanese monkey adult males and females show remarkable spatial proximity and frequent exchanges of social behaviors. It is suggested that some kind of “affinity” exists between them. Females obtain much unilateral benefit from “proximity effects”; even lowranking females can dominate high-ranking females as long as they stay nearby their “affinitive” males. Males acquire female followers in return. Mating relations and female mother-daughter relations play important roles in forming new “affinitive relations.” Once monkeys have formed “affinitive relations,” however, they seldom mate with each other, as if they were kin-related. Therefore, the acquisition of female followers appears inconsistent with a male's strategy for reproducing many genes in the next generation. This study was financed partly by the Cooperative Research Fund of the Primate Research Institute, Kyoto University. The outline of this paper has already been published inTakahata (1980b).     

T<Subscript>2</Subscript>-weighted μMRI and Evoked Potential of the Visual System Measurements During the Development of Hypomyelinated Transgenic Mice

Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 × 117 × 70 μm) magnetic resonance (μMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli–mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted μMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The μMRI data indicated clear, global hypomyelination during the period of peak myelination (21–42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These μMRI data correlated well with [Campagnoni AT (1995) “Molecular biology of myelination”. In: Ransom B, Kettenmann H (eds) Neuroglia—a Treatise. Oxford University Press, London, pp 555–570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41–89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197–224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain. Special Issue in honor of Anthony and Celia Campagnoni     

“Girney” vocalizations among Japanese macaque females: Context and function

One vocalization in the Japanese macaque (Macaca fuscata) system of communication is the “girney.” Previous studies indicated that the “girney” is used for short range communication and that it tends to occur when subordinate animals approach and groom dominant ones and when females without infants approach females who have infants. Data were collected on the social behavior of adult female Japanese monkeys of the Arashiyama-A troop in Texas in order to test those results. The study indicates that “girneys” are the most frequently occurring vocalizations of females during and following the birth season and that they occur primarily in two contexts. Those are the proximity of a female to another female with a new infant and the proximity of a lower ranking animal to a higher ranking one. The contexts are ones in which the risk of aggression is high, and the “girneys” appear to function as appeasement gestures to reduce the risk.     

“Silenced” polydendrocytes: a new cell type within the oligodendrocyte progenitor cell population?

Oligodendrocyte progenitor cells (OPCs) were first described more than two decades ago. Novel labeling techniques have shown them to be cells with more than just progenitor functions, with their classification as a fourth glial cell type in addition to astrocytes, oligodendrocytes, and microglial cells. Another term used for this cell type is polydendrocytes, owing to both their morphology and to the evolving knowledge about their diverse functions. Recently, an exclusive hallmark of neurons—the generation of action potentials—became debatable, because a subset of polydendrocytes was reported to generate action potentials in response to adequate stimuli. The new technique of inducible reporter gene expression has brought new insights into the fate and function of polydendrocytes. In recent studies, so-called “silenced” OPCs were detected in cortical tissue, and which underwent proliferation with subsequent cell cycle exit, but without any signs of differentiation. Within this review, we focus on the identification of this new subset of polydendrocytes and their possible functions within cortical networks.     

Dynamic analysis,with feedback characterization,of hybrid human musculoskeletal frameworks by the linegraph-flowgraph procedure

The dynamic response of human musculo-skeletal framework is treated by (i) idealization of the musculo-skeletal framework as hybrid structural networks possessing feedback characteristics and then (ii) employing linegraph-flowgraph procedures for the feedback characterization of the hybrid structural networks. Topological procedures are used in which a “tree” of a network furnishes the skeleton upon which the “linkage” (muscle representing) members provide interaction. Feedback characterization (representing the sensitivity of the skeletal members to the tensile forces) is defined, between the internal “linkage” and “tree” members, by means of the flowgraph. Mikusinski operational calculus is used to facilitate representation of inertia effects by dynamic feedback characterization, with inclusion of initial conditions.     

Synchrony and Asynchrony for Neuronal Dynamics Defined on Complex Networks

We describe and analyze a model for a stochastic pulse-coupled neuronal network with many sources of randomness: random external input, potential synaptic failure, and random connectivity topologies. We show that different classes of network topologies give rise to qualitatively different types of synchrony: uniform (Erdős–Rényi) and “small-world” networks give rise to synchronization phenomena similar to that in “all-to-all” networks (in which there is a sharp onset of synchrony as coupling is increased); in contrast, in “scale-free” networks the dependence of synchrony on coupling strength is smoother. Moreover, we show that in the uniform and small-world cases, the fine details of the network are not important in determining the synchronization properties; this depends only on the mean connectivity. In contrast, for scale-free networks, the dynamics are significantly affected by the fine details of the network; in particular, they are significantly affected by the local neighborhoods of the “hubs” in the network.     

Californian Salt-Marsh Vegetation: An Improved Model of Spatial Pattern

Although tidal wetland vegetation patterns are typically related to elevation, we hypothesized that the vertical range of a species may shift where the topography is more heterogeneous. We examined plant species occurrences in relation to elevation, proximity to the bay, and proximity to tidal creeks at a near-pristine wetland in San Quintín Bay, Baja California, Mexico. At the whole-wetland scale, most species occurred primarily within a 30-cm elevation band (the marsh plain). However, Spartina foliosa occurred only at the bayward margin, even though “suitable” elevations were present further inland. A similar pattern was found in San Diego Bay. At the microtopographic scale, three species on the marsh plain were strongly influenced by elevation, whereas four species responded to both elevation and proximity to tidal creeks. The latter species tended to “avoid” the lower 10 cm of the marsh plain except near a tidal creek. Species richness was thus greater (by 0.6 species at the lowest 10-cm class) at the tidal creek margin. Better drainage near creeks is the hypothesized cause. Our results help explain why species that are transplanted to constructed wetlands do not always grow at the full range of elevations they occupy in natural wetlands. We recommend that species be introduced to their modal elevation (determined from nearby reference marshes) and that salt-marsh construction designs include topographic heterogeneity (complex tidal creek networks). The analysis of broad-scale and fine-scale patterns of occurrence also suggests new habitat nomenclature. Elevation-based terms (“low,”“middle,” and “high” marsh) should be replaced by a system that considers elevation, landscape position, and conspicuous species. We suggest three habitat designations: (a) the high marsh—a 30- to 70-cm elevation range with Salicornia subterminalis; (b) the marsh plain—a 30-cm elevation range with heterogeneous topography and up to nine common species; and (c) cordgrass habitat—the bayward portion of the marsh plain and lower elevations, all occupied by Spartina foliosa. Although these habitats do not have discrete boundaries, separate terms are needed for wetland restoration plans and these designations will improve recognition that vegetation patterns respond to horizontal, as well as vertical, position.