Microglia Instruct SubVentricular Zone NeuroGenesis
Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP 2nd, Scheffler B, Steindler DA
Glia 2006 Dec;54(8):815-25
University of Florida, Department of NeuroScience, McKnight Brain Institute, Gainesville, FL 32610, USA
Microglia are increasingly implicated as a source of Non-Neural regulation of postnatal NeuroGenesis and Neuronal development.
To evaluate better the contributions of Microglia to Neural Stem Cells (NSCs) of the SubVentricular NeurAxis, we employed an adherent culture system that models the continuing proliferation and differentiation of the dissociated NeuroPoietic SubVentricular tissues.
In this model, NeuroPoietic Cells retain the ability to self-renew and form multipotent Neurospheres, but progressively lose the ability to generate committed Neuroblasts with continued culture.
NeuroGenesis in highly expanded NSCs can be rescued by coculture with Microglial Cells Or Microglia-conditioned medium.
Indicating that Microglia provide secreted factor(s) essential for NeuroGenesis, but not NSC maintenance, self-renewal, or propagation.
Our findings suggest an instructive role for Microglial Cells in contributing to postnatal NeuroGenesis in the largest Neurogenic niche of the mammalian Brain.
(c) 2006 Wiley-Liss, Inc.
Multiple Sclerosis And Alzheimer's Disease
Dal Bianco A, Bradl M, Frischer J, Kutzelnigg A, Jellinger K, Lassmann H
Ann Neurol 2008 Feb;63(2):174-83
Medical University of Vienna, Center for Brain Research, Austria
Chronic inflammation with Microglia activation is thought to play a major role in the formation or clearance of Alzheimer's Disease (AD) lesions, as well as in the induction of DeMyelination in Multiple Sclerosis (MS).
In MS, the cortex is severely affected by chronic, long-lasting inflammation, Microglia activation, and DeMyelination. To what extent chronic inflammation in the Cortex of MS patients influences the development of AD lesions is so far unresolved.
The study was performed on autopsy tissue of 45 MS cases, 9 AD cases, and 15 control subjects. We analyzed Lymphocyte and Plasma Cell infiltration in relation to Microglia activation, to the presence of beta-Amyloid plaques and (AT8+) NeuroFibrillary tangles, and to Myelin pathology.
Profound Microglia activation, determined by a broad spectrum of markers, was found in both MS and AD Cortices, and the patterns of Microglia activation were closely similar.
Microglia activation in MS Cortex, in contrast with that in AD and control cortex, correlated with Lymphocyte and Plasma-Cell infiltrates in the Meninges.
MS cases older than 64 years experienced development of AD pathology in comparable incidence as seen in the course of normal aging.
The density of beta-Amyloid plaques and NeuroFibrillary tangles did not differ between DMyelinated and NonDeMyelinated Cortical areas.
Our data suggest that Microglia activation in the MS Cortex alone has little or no influence on the development of Cortical AD pathology.
Elevated Activity And Microglial Expression Of MyelopPerOxidase In DeMyelinated Cerebral Cortex In Multiple Sclerosis
Gray E, Thomas TL, Betmouni S, Scolding N, Love S
Brain Pathol 2008 Jan;18(1):86-95
University of Bristol Institute of Clinical NeuroScience, Glial Cell Biology Laboratories, Frenchay Hospital, Bristol, UK
Recent studies have revealed extensive Cortical DeMyelination in patients with Progressive Multiple Sclerosis (MS).
DeMyelination in Gray Matter lesions is associated with activation of Microglia. Macrophages and Microglia are known to express MyeloPerOxidase (MPO) and generate Reactive Oxygen Species during Myelin Phagocytosis in the White Matter.
In the present study we examined the extent of Microglial activation in the Cerebral Cortex and the relationship of Microglial activation and MPO activity to Cortical DeMyelination.
Twenty-one cases of NeuropPathologically confirmed Multiple Sclerosis, with 34 Cortical lesions, were used to assess Microglial activation.
HLA-DR immunolabeling of activated Microglia was significantly higher in DeMyelinated MS Cortex than control Cortex and, within the MS cohort, was significantly greater within Cortical Lesions than in matched Non-DeMyelinated areas of Cortex.
In homogenates of MS Cortex, Cortical DeMyelination was associated with significantly elevated MPO activity.
ImmunoHistoChemistry revealed MPO in CD68+ Microglia within Cortical plaques, particularly toward the edge of the plaques, but not in Microglia in adjacent Non-DeMyelinated Cortex.
Cortical DeMyelination in MS is associated with increased activity of MPO, which is expressed by a CD68+ subset of activated Microglia, suggesting that Microglial production of Reactive Oxygen Species is likely to be involved in Cortical DeMyelination.
Elevated MyeloPerOxidase Activity In White Matter In Multiple Sclerosis
Gray E, Thomas TL, Betmouni S, Scolding N, Love S
Neurosci Lett 2008 Aug 15
University of Bristol Institute of Clinical NeuroSciences, MS Laboratories, Burden Centre, Frenchay Hospital, Bristol BS16 1JB, United Kingdom
Recent studies have revealed extensive Axonal Damage in patients with Progressive Multiple Sclerosis (MS).
Axonal Damage can be caused by a plethora of factors including the release of ProteoLytic Enzymes and CytoToxic Oxidants by activated Immune Cells and Glia within the lesion.
Macrophages and Microglia are known to express MyeloPerOxidase (MPO) and generate Reactive Oxygen Species during Myelin Phagocytosis in the White Matter.
In the present study we have measured MPO levels in post-mortem homogenates of DeMyelinated and Non-DeMyelinated regions of White Matter from nine patients with MS and seven controls, and assessed MPO ImmunoReactivity within MS Brain.
In homogenates of MS White Matter, DeMyelination was associated with significantly elevated MPO activity when compared to controls.
ImmunoHistoChemistry showed MPO to be expressed mainly by Macrophages within and adjacent to plaques.
DeMyelination in MS is associated with increased activity of MPO, suggesting that this production of Reactive Oxygen Species may contribute to Axonal injury within plaques.