Biomedical subjects

Shucui Jiang

Publications and source records attributed to Shucui Jiang.

6 recordsLinked to original sources

PubMed2007

Guanosine inhibits CD40 receptor expression and function induced by cytokines and beta amyloid in mouse microglia cells.

Growing evidence implicates CD40, a member of the TNFR superfamily, as contributing to the pathogenesis of many neurodegenerative diseases. Thus, strategies to suppress its expression may be of benefit in those disorders. To this aim, we investigated the effect of guanosine, a purine nucleoside that exerts neurotrophic and neuroprotective effects. CD40 expression and function are increased by exposure of mouse microglia cultures or the N9 microglia cell line to IFN-gamma (10 ng/ml) plus TNF-alpha (50 ng/ml) or beta amyloid (Abeta) peptide (Abeta(1-42); 500 nM). Culture pretreatment with guanosine (10-300 microM), starting 1 h before cytokine or Abeta addition, dose-dependently inhibited the CD40-induced expression as well as functional CD40 signaling by suppressing IL-6 production promoted by IFN-gamma/TNF-alpha challenge in the presence of CD40 cross-linking. Moreover, guanosine abrogated IFN-gamma-induced phosphorylation on Ser(727) and translocation of STAT-1alpha to the nucleus as well as TNF-alpha-/Abeta-induced IkappaBalpha and NF-kappaB p65/RelA subunit phosphorylation, thus inhibiting NF-kappaB-induced nuclear translocation. Guanosine effects were mediated by an increased phosphorylation of Akt, a PI3K downstream effector, as well as of ERK1/2 and p38 in the MAPK system, because culture pretreatment with selective ERK1/2, p38 MAPK, and PI3K antagonists (U0126, SB203580, or LY294002, respectively) counteracted guanosine inhibition on IFN-gamma/TNF-alpha-induced CD40 expression and function as well as on STAT-1alpha or NF-kappaB nuclear translocation. These findings suggest a role for guanosine as a potential drug in the experimental therapy of neuroinflammatory/neurodegenerative diseases, particularly Alzheimer's disease.

Amyloid beta-Peptides↗

PubMed2004

Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats.

Enteric glia share morphological, biochemical, and functional properties with astrocytes. Thus, like astrocytes, transplantation of enteric glia into the central nervous system (CNS) might facilitate the development of the characteristics of the blood brain barrier (BBB) in endothelial cells. This study explored this possibility by examining barrier formation after implantation into the spinal cord of rats. Phaseolus vulgaris leucoagglutin (PHAL)-treated enteric glia suspensions were injected into the spinal cord at the T11-T12 level of adult Wistar female rats. Control animals were injected with either 3T3 fibroblast, glioma C6 cells, or culture medium. Evan's blue, a dye excluded by the BBB, was injected intravenously from 1 week to 2 months after implantation. Leakage of dye was determined macroscopically and the ultrastructure of the capillaries was examined. During the first week leakage of dye correlated ultrastructurally with predominantly non-overlapping endothelial cell junctions, even with clefts between adjacent cells. Tight junctions were fully formed by 2 months and no dye leaked. Electron microscopic analysis showed that enteric glia had end-feet in close contact with endothelial cells. In contrast, the injection sites in all control animals leaked dye until 2 months, and most of the tight junctions that did form were incomplete. Furthermore, most 3T3 or C6 control cells had died at 2 months and those that survived, unlike enteric glia, had no anatomical relationship to blood vessels. These data demonstrate that implantation of enteric glia accelerates the formation of the characteristics of the BBB in spinal cord capillaries.

Animals↗

PubMed2003

Guanosine promotes myelination and functional recovery in chronic spinal injury.

Functional loss after spinal cord injury (SCI) is caused, in part, by demyelination of axons surviving the trauma. Administration of guanosine (8 mg/kg/day, i.p.) for 7 consecutive days, starting 5 weeks after moderate SCI in rats, improved locomotor function and spinal cord remyelination. Myelinogenesis was associated with an increase in the number of mature oligodendrocytes detected in guanosine-treated spinal cord sections in comparison with controls. These data indicate that guanosine-induced remyelination resulted, at least in part, from activation of endogenous oligodendrocyte lineage cells. These findings may have significant implications for chronic demyelinating diseases.

Animals↗

PubMed2003

Enteric glia promote functional recovery of CTM reflex after dorsal root transection.

Transected dorsal root axons of adult rats can be induced to regenerate through the normally non-permissive environment of the dorsal root entry zone (DREZ) into the spinal cord by implanting enteric glia (EG) into the DREZ. We have now examined whether the regenerating central axons make functional connections by studying the return of function of a behavioral response, the cutaneous trunci muscle (CTM) reflex. Implantation of EG into the spinal cord DREZ led to functional recovery of the CTM reflex in 82%, 72% and 70% of animals 1, 2 and 3 months, respectively, after injury. In contrast, the CTM reflex did not recover in animals implanted with 3T3 or C6 glioma cells or with vehicle only.

3T3 Cells↗

PubMed2003

Enteric glia promote regeneration of transected dorsal root axons into spinal cord of adult rats.

After spinal cord injury axonal regeneration is poor, but may be enhanced by the implantation of olfactory ensheathing glia (OEG). Enteric glia (EG) share many properties of OEG. Transected dorsal root axons normally do not regenerate through the central nervous system myelin into the spinal cord. We tested whether EG, like OEG, could promote regeneration in this paradigm. Three weeks after EG implantation, numerous regenerating dorsal root axons reentered the spinal cord. Ingrowth of dorsal root axons was observed using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal gray commissure. No axonal ingrowth was observed in control animals, indicating that transplanted EG enabled regeneration of the injured dorsal root axons into the adult spinal cord. Thus, EG implantation may be beneficial in promoting axonal growth after central nervous system injury.

3T3 Cells↗

PubMed2002

A method for purifying enteric glia from rat myenteric plexus.

The enteric nervous system is a large and complex division of the peripheral nervous system. The glia associated with it share some characteristics with the olfactory-ensheathing glia, astrocytes and Schwann cells. To facilitate studies of rat enteric glia, we have developed a method for preparing them in large quantities with a high degree of homogeneity. The enteric glia were isolated from the small intestine of Wistar rats by enzymatic digestion with dispase. The cell isolate was added to a mitotically arrested layer of 3T3 cells. Subsequent separation of the enteric glia from the 3T3 cells was done enzymatically, with unavoidable loss of many enteric glia and potential contamination of enteric glia cultures with the 3T3 cells. Therefore, 3T3 cells were cultured in Nunc 0.2-microm tissue culture inserts that could be readily removed from the wells when no longer needed. There was no loss of the enteric glia. The cultures consisted entirely of GFAP-labeled cells, presumptive enteric glia. This method permits the culturing of large numbers of highly purified enteric glia without the use of expensive growth factors and complement-mediated cytolysis.

3T3 Cells↗