Jun E. Yoshino

Bio: Jun E. Yoshino is an academic researcher from Colgate University. The author has contributed to research in topics: Schwann cell & Neuroglia. The author has an hindex of 7, co-authored 9 publications receiving 1625 citations. Previous affiliations of Jun E. Yoshino include Uniformed Services University of the Health Sciences.

Astrogliosis during acute and chronic cuprizone demyelination and implications for remyelination

Abstract: In multiple sclerosis, microglia/macrophage activation and astrocyte reactivity are important components of the lesion environment that can impact remyelination. The current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum. Importantly, periods of recovery after acute or chronic cuprizone demyelination are examined to compare conditions of efficient versus limited remyelination, respectively. Microglial activation attenuates after early demyelination. In contrast, astrocyte reactivity persists throughout demyelination and a 6-week recovery period following either acute or chronic demyelination. This astrocyte reaction is characterized by (a) early proliferation, (b) increased expression of GFAP (glial fibrillary acidic protein), Vim (vimentin), Fn1 (fibronectin) and CSPGs (chondroitin sulphate proteoglycans) and (c) elaboration of a dense network of processes. Glial processes elongated in the axonal plane persist throughout lesion areas during both the robust remyelination that follows acute demyelination and the partial remyelination that follows chronic demyelination. However, prolonged astrocyte reactivity with chronic cuprizone treatment does not progress to barrier formation, i.e. dense compaction of astrocyte processes to wall off the lesion area. Multiple candidate growth factors and inflammatory signals in the lesion environment show strong correlations with GFAP across the acute cuprizone demyelination and recovery time course, yet there is more divergence across the progression of chronic cuprizone demyelination and recovery. However, differential glial scar formation does not appear to be responsible for differential remyelination during recovery in the cuprizone model. The astrocyte phenotype and lesion characteristics in this demyelination model inform studies to identify triggers of non-remyelinating sclerosis in chronic multiple sclerosis lesions.

Subcellular Distribution of Sulfated Glucuronyl Glycolipids in Human Peripheral Motor and Sensory Nerves.

Abstract: Sulfated glucuronyl glycolipids (SGGL) have been implicated as important target antigens in patients with demyelinating polyneuropathy and IgM paraproteinemia. Sulfated glucuronyl paragloboside (SGPG), a major species of SGGL, was identified in the subcellular fractions of human peripheral motor and sensory nerves using a simple and quantitative method. SGPG was found to be concentrated in the myelin-enriched fractions of both motor and sensory nerves (1.3 +/- 0.3 and 1.5 +/- 0.4 mg/mg protein, respectively), whereas its concentration was 0.9 +/- 0.2 and 1.8 +/- 0.6 mg/mg protein in the axolemma-enriched fractions of motor and sensory nerves, respectively. Our finding that SGPG is more abundant in the human sensory nerve axolemma-enriched fraction may account for the clinical and pathological observations that the lesions are more heavily concentrated in the sensory nerve than in other parts of the nerve tissues in this disorder. Copyright 1994 S. Karger AG, Basel

Axonal regulation of Schwann cell glycolipid biosynthesis.

Abstract: Schwann cell biosynthesis of glycolipids was studied by in vitro incorporation of [3H]galactose into neonatal rat sciatic nerves before and after endoneurial explant culture and in culture of purified Schwann cells. In neonatal nerves prior to culture, [3H]galactose was actively incorporated into galactocerebrosides (GalCe), monogalactosyl diacylglycerol (MGDG), and the sulfatides (Su). In contrast, the incorporation of [3H]galactose into MGDG, GalCe, and Su was nearly undetected in endoneurial explants after 4 days in vitro (div). Instead, there was increased3H-labeling of glucocerebrosides (GlcCe) and its homologues, with tetrahexosylceramides (GL-4) being a major product, which continued through 8 div. This shift in glycolipid biosynthesis was further demonstrated in the purified Schwann cell cultures. These observations, together with our early findings in the permanent transection paradigm support a direct role of axons in specifying Schwann cell biosynthesis of the GalCe, MGDG, and Su and that the absence of this Schwann cell-axon interaction results in the phenotypic expression of glucocerebroside homologues by the Schwann cell.

Proliferation and differentiation of a transfected Schwann cell line is altered by an artificial basement membrane.

Abstract: Rapidly dividing transfected Schwann cells were grown on Matrigel, a reconstituted basement membrane gel. Matrigel decreased the proliferation of the cells by 75% when compared to sister cultures that were grown on an untreated plastic substrate. Some transfected cells plated onto a Matrigel substrate formed colonies similar to that observed when the cells were plated on a plastic substrate. Additionally, many cells on Matrigel assembled themselves into fascicles projecting away from the colonies. These fascicles were composed of transfected Schwann cells that had assumed a bipolar appearance reminiscent of quiescent secondary Schwann cells in culture. Transfected cells grown on Matrigel contained approximately 10-fold less glial fibrillary acidic protein when compared to sister cultures grown on an untreated plastic substrate. By indirect immunofluorescence laminin immunoreactivity appeared as globules within the cytoplasm of the cells which were cultured on a plastic substrate. However, cells that were grown on the Matrigel substrate appear to organize laminin in a linear array around themselves. These results demonstrate that the presence of an artificial basement membrane alters the morphology, rate of proliferation, and state of differentiation of a transfected Schwann cell line.

The cellular and molecular basis of peripheral nerve regeneration.

Abstract: Functional recovery from peripheral nerve injury and repair depends on a multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival after axotomy is a prerequisite for regeneration and is facilitated by an array of trophic factors from multiple sources, including neurotrophins, neuropoietic cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting mode to a growth mode and express growth-associated proteins, such as GAP-43, tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all of which have the potential to promote axonal regeneration. Axonal sprouts must reach the distal nerve stump at a time when its growth support is optimal. Schwann cells in the distal stump undergo proliferation and phenotypical changes to prepare the local environment to be favorable for axonal regeneration. Schwann cells play an indispensable role in promoting regeneration by increasing their synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N-cadherin, and L2/HNK-1, by elaborating basement membrane that contains many extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by producing many neurotrophic factors and their receptors. However, the growth support provided by the distal nerve stump and the capacity of the axotomized neurons to regenerate axons may not be sustained indefinitely. Axonal regenerations may be facilitated by new strategies that enhance the growth potential of neurons and optimize the growth support of the distal nerve stump in combination with prompt nerve repair.

Longitudinal Development of Human Brain Wiring Continues from Childhood into Adulthood

Abstract: Healthy human brain development is a complex process that continues during childhood and adolescence, as demonstrated by many cross-sectional and several longitudinal studies. However, whether these changes end in adolescence is not clear. We examined longitudinal white matter maturation using diffusion tensor tractography in 103 healthy subjects aged 5–32 years; each volunteer was scanned at least twice, with 221 total scans. Fractional anisotropy (FA) and mean diffusivity (MD), parameters indicative of factors including myelination and axon density, were assessed in 10 major white matter tracts. All tracts showed significant nonlinear development trajectories for FA and MD. Significant within-subject changes occurred in the vast majority of children and early adolescents, and these changes were mostly complete by late adolescence for projection and commissural tracts. However, association tracts demonstrated postadolescent within-subject maturation of both FA and MD. Diffusion parameter changes were due primarily to decreasing perpendicular diffusivity, although increasing parallel diffusivity contributed to the prolonged increases of FA in association tracts. Volume increased significantly with age for most tracts, and longitudinal measures also demonstrated postadolescent volume increases in several association tracts. As volume increases were not directly associated with either elevated FA or reduced MD between scans, the observed diffusion parameter changes likely reflect microstructural maturation of brain white matter tracts rather than just gross anatomy.