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Neil J Scolding

Publications and source records attributed to Neil J Scolding.

5 recordsLinked to original sources
PubMed2006

Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions.

Following inflammatory demyelination in multiple sclerosis (MS), partial remyelination occurs. Studies in rodents have indicated that oligodendrocyte precursor cells (OPCs) are responsible for this remyelination. Rodent OPCs are identified in situ with antibodies against platelet-derived growth factor alpha receptor (PDGFalphaR) and NG2 chondroitin sulfate proteoglycan. In human CNS tissue, studies of NG2 and PDGFalphaR expression are limited and controversy exists as to whether these molecules are specific OPC markers. This study has investigated whether PDGFalphaR and NG2 are co-expressed on OPCs in human CNS, and whether OPCs are associated with remyelination in MS. MS brain tissue was examined for PDGFalphaR and NG2 immunoreactivity and for expression of NG2 mRNA by in situ hybridisation. Putative OPCs, expressing both NG2 and PDGFalphaR, were present within normal-appearing white matter and within areas of active demyelination in MS, but not in chronic silent lesions. They were also seen in association with remyelination in MS tissue and with developmental myelination in human spinal cord. NG2+ cells that did not express PDGFalphaR were also detected. Given their lack of reactivity with microglial or astrocyte markers, these NG2+/PDGFalphaR- cells probably represented more mature OPCs that had lost PDGFalphaR expression. The distribution of OPCs observed in this study strongly suggests these cells are potential sources of remyelinating oligodendrocytes in active lesions in MS.

Antigens↗
PubMed2005

Abeta-related angiitis: primary angiitis of the central nervous system associated with cerebral amyloid angiopathy.

Idiopathic or primary angiitis of the CNS (PACNS) and cerebral amyloid angiopathy (CAA) are unusual vasculopathies generally regarded as unrelated disorders. A few case reports have, however, described granulomatous angiitis in patients with sporadic, amyloid beta peptide (Abeta)-related CAA. Here we describe the clinical, neuroradiological and neuropathological features of nine patients with Abeta-related angiitis (ABRA). Combining these with the individual case reports drawn from the literature has allowed us to define ABRA as a clinical entity and to compare its features with those of PACNS. The mean age of presentation of ABRA (67 years) is higher than that of PACNS but lower than that of sporadic non-inflammatory Abeta-related CAA. Alterations in mental status (59%), headaches (35%), seizures and focal neurological deficits (24%) are common. Hallucinations are a presenting manifestation in 12% of cases. Most patients have white matter hyperintensities on MRI but these are of similar appearance to those in PACNS. Cerebrospinal fluid usually shows modest elevation of protein and pleocytosis. Neuropathology reveals angiodestructive inflammation, often granulomatous, and meningeal lymphocytosis. Abeta is consistently present in abundance in affected blood vessels but usually scanty within the parenchyma of the cerebral cortex. However, the cortex includes numerous activated microglia, occasionally in a plaque-like distribution and containing cytoplasmic Abeta. The cerebral white matter shows patchy gliosis and rarefaction, in some cases marked. Our findings (i) help to dissect one separate clinicopathological entity from what is likely to be a spectrum of primary angiitides of the CNS; (ii) have important therapeutic implications for one category of patients with amyloid-related vasculopathy; and (iii) may provide valuable insights into the development of amyloid-associated inflammation, of relevance not only to ABRA but also to Abeta-immunization-related encephalitis and to Alzheimer's disease.

Aged↗
PubMed2004

Metabotropic glutamate receptors are expressed in adult human glial progenitor cells.

Glial precursor cells (GPCs) are present in the adult human central nervous system (CNS) and they can be isolated and maintained in culture for in vitro studies. This study analysed expression of mGluR3 and mGluR5 metabotropic glutamate receptor (mGluR) mRNAs in GPCs. A2B5 surface antigen positive GPCs were isolated using immunomagnetic selection from dissociated temporal lobe subcortical white matter cells. The separated GPCs were maintained in cultures and characterised by immunoreactivity for the differentiation markers A2B5 and human platelet-derived growth factor-alpha receptor (PDGFalphaR). Reverse transcription followed by multiplex PCR analysis showed that the GPCs expressed both mGluR3 and mGluR5a mRNAs. Double immunostaining for glial progenitor markers and mGluR5 proteins demonstrated that all A2B5 and PDGFalphaR-positive cells were also positive for mGluR5. The results indicate that GPCs present in the adult human CNS express mGluR3 and mGluR5a. These neurotransmitter receptors may be involved in the proliferation and differentiation of glial cells.

Animals↗
PubMed2004

S1P and LPA trigger Schwann cell actin changes and migration.

The processes by which a Schwann cell (SC) migrates towards, wraps around and, in some cases, myelinates an axon are incompletely understood. The complex morphological rearrangements involved in these events require fundamental changes in the actin cytoskeleton. Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are two modulators of the actin cytoskeleton, and receptors for these signalling lipids are expressed on SCs at the time of differentiation. Previous work has revealed a role for LPA in SC survival, morphology and differentiation, but the effects of S1P have received less attention. Here we show that S1P and LPA both cause major rearrangements to the actin cytoskeleton in primary rat SCs and the SCL4.1/F7 rat SC line. S1P and LPA caused formation of lamellipodia and a circular geodesic actin network. We also show that S1P and LPA increased cell migration. The small GTPases RhoA and Rac1 were both activated by S1P/LPA treatment, but the actin rearrangements were dependent on Rac1 and not RhoA. These effects of S1P/LPA could be mimicked by SCL4.1/F7 cell-conditioned medium, which was found to contain S1P. Reduction in cellular synthesis of S1P by adding the sphingosine kinase inhibitor dimethyl sphingosine during medium conditioning reduced the ability of conditioned medium to cause actin rearrangements. These results support a role for S1P as an autocrine signal regulating the actin cytoskeleton during Schwann cell development.

Actins↗