Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system

2000 ◽  
Vol 278 (5) ◽  
pp. R1275-R1281 ◽  
Author(s):  
Irene R. Pelá ◽  
Márcia E. S. Ferreira ◽  
Miriam C. C. Melo ◽  
Carlos A. A. Silva ◽  
Márcio M. Coelho ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Third Ventricle ◽  
Platelet Derived Growth Factor ◽  
Febrile Response ◽  
The Central Nervous System ◽  
Factor Α ◽  
Colonic Temperature

Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289–293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3–4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-α, interleukin-1β, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

scholarly journals Snapin deficiency is associated with developmental defects of the central nervous system

2010 ◽  
Vol 31 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Bing Zhou ◽  
Yi-Bing Zhu ◽  
Lin Lin ◽  
Qian Cai ◽  
Zu-Hang Sheng
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Protein Quality ◽  
Third Ventricle ◽  
Critical Role ◽  
Developmental Defects ◽  
Lysosomal Function ◽  
Quality Control Process ◽  
The Central Nervous System

The autophagy–lysosomal pathway is an intracellular degradation process essential for maintaining neuronal homoeostasis. Defects in this pathway have been directly linked to a growing number of neurodegenerative disorders. We recently revealed that Snapin plays a critical role in co-ordinating dynein-driven retrograde transport and late endosomal–lysosomal trafficking, thus maintaining efficient autophagy–lysosomal function. Deleting snapin in neurons impairs lysosomal proteolysis and reduces the clearance of autolysosomes. The role of the autophagy–lysosomal system in neuronal development is, however, largely uncharacterized. Here, we report that snapin deficiency leads to developmental defects in the central nervous system. Embryonic snapin−/− mouse brain showed reduced cortical plates and intermediate zone cell density, increased apoptotic death in the cortex and third ventricle, enhanced membrane-bound LC3-II staining associated with autophagic vacuoles and an accumulation of polyubiquitinated proteins in the cortex and hippocampus. Thus our results provide in vivo evidence for the essential role of late endocytic transport and autophagy–lysosomal function in maintaining neuronal survival and development of the mammalian central nervous system. In addition, our study supports the existence of a functional interplay between the autophagy–lysosome and ubiquitin–proteasome systems in the protein quality-control process.

The Biological Role of Truncated Insulin-like Growth Factor-1 and the Tripeptide GPE in the Central Nervous System

1993 ◽  
Vol 692 (1 The Role of I) ◽  
pp. 183-191 ◽  
Author(s):  
VICKI R. SARA ◽  
C. CARLSSON-SKWIRUT ◽  
K. DRAKENBERG ◽  
M. B. GIACOBINI ◽  
L. HÅKANSSON ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Biological Role ◽  
Insulin Like Growth Factor ◽  
The Central Nervous System

A role for platelet-derived growth factor in normal gliogenesis in the central nervous system

Cell ◽  
1988 ◽  
Vol 53 (2) ◽  
pp. 309-319 ◽  
Author(s):  
William D. Richardson ◽  
Nigel Pringle ◽  
Michael J. Mosley ◽  
Bengt Westermark ◽  
Monique Dubois-Dalcg
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Platelet Derived Growth Factor ◽  
The Central Nervous System

scholarly journals The role of the surface on microglia function: implications for central nervous system tissue engineering

2015 ◽  
Vol 12 (103) ◽  
pp. 20141224 ◽  
Author(s):  
Liliana R. Pires ◽  
Daniela N. Rocha ◽  
Luigi Ambrosio ◽  
Ana Paula Pêgo
Keyword(s):  
Tissue Engineering ◽  
Central Nervous System ◽  
Nervous System ◽  
Culture Media ◽  
Giant Cells ◽  
Trimethylene Carbonate ◽  
Flat Surfaces ◽  
The Central Nervous System ◽  
Factor Α

In tissue engineering, it is well accepted that a scaffold surface has a decisive impact on cell behaviour. Here we focused on microglia—the resident immune cells of the central nervous system (CNS)—and on their response to poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) fibrous and flat surfaces obtained by electrospinning and solvent cast, respectively. This study aims to provide cues for the design of instructive surfaces that can contribute to the challenging process of CNS regeneration. Cell morphology was evidently affected by the substrate, mirroring the surface main features. Cells cultured on flat substrates presented a round shape, while cells with elongated processes were observed on the electrospun fibres. A higher concentration of the pro-inflammatory cytokine tumour necrosis factor-α was detected in culture media from microglia on fibres. Still, astrogliosis is not exacerbated when astrocytes are cultured in the presence of microglia-conditioned media obtained from cultures in contact with either substrate. Furthermore, a significant percentage of microglia was found to participate in the process of myelin phagocytosis, with the formation of multinucleated giant cells being observed only on films. Altogether, the results presented suggest that microglia in contact with the tested substrates may contribute to the regeneration process, putting forward P(TMC-CL) substrates as supporting matrices for nerve regeneration.

scholarly journals Loss of PRMT5 promotes PDGFRα degradation during oligodendrocyte differentiation and myelination

2018 ◽  
Author(s):  
Sara Calabretta ◽  
Gillian Vogel ◽  
Zhenbao Yu ◽  
Karine Choquet ◽  
Lama Darbelli ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Arginine Methylation ◽  
Platelet Derived Growth Factor ◽  
Oligodendrocyte Differentiation ◽  
The Central Nervous System ◽  
Cns Myelination

SummaryPlatelet derived growth factor receptor α (PDGFRα) signaling is required for proliferation, commitment and maintenance of oligodendrocyte (OL) precursor cells (OPCs). PDGFRα signaling promotes OPC homeostasis and its attenuation signals OPC differentiation and maturation triggering the onset of myelination of the central nervous system (CNS). The initial steps of how PDGFRα signaling is attenuated are still poorly understood. Herein we show that decreased Protein Arginine MethylTransferase5 (PRMT5) expression, as occurs during OPC differentiation, is involved in the down-regulation of PDGFRα by modulating its cell surface bioavailability leading to its degradation in a Cbldependent manner. Mechanistically, loss of arginine methylation at R554 of the PDGFRα intracellular domain reveals a masked Cbl binding site at Y555. Physiologically, depletion of PRMT5 in OPCs results in severe CNS myelination defects. We propose that decreased PRMT5 activity initiates PDGFRα degradation to promote OL differentiation. More broadly, inhibition of PRMT5 may be used therapeutically to manipulate PDGFRα bioavailability.

Sign in / Sign up

Export Citation Format

Share Document