The origin of ramified microglia has been a longstanding controversial issue, with 4 major schools of thought, which state that they are derived (1) from invasion of mesodermal pial elements, (2) from neuroectodermal matrix cells together with the macroglia, (3) from pericytes, and (4) from invasion of monocytes in early development. This paper is in support of the last-mentioned hypothesis. It is known that ramified microglial cells do not divide under normal circumstances, and since our studies in the corpus callosum have shown that these cells do not appear until the fifth postnatal day, it is reasoned that they must be derived from some preexisting mitotically active cells. The putative precursor is the preponderant amoeboid microglia in the same region. Our experimental studies with the carbon labelling technique have demonstrated for the first time that blood monocytes invade into the early postnatal brain to become amoeboid microglia, which then differentiate into ramified microglia. Just like other tissue macrophages, the monocyte-derived amoeboid microglia exhibit features indicative of phagocytic activities. These include the content of hydrolytic enzymes, uptake of carbon, and a characteristic surface morphology, as seen by scanning electron microscopy. The transformation of amoeboid microglia into ramified microglia, which occurs between the second and third postnatal week, is considered to be a regressive phenomenon, as shown by the diminution of their content of hydrolytic enzymes and the downregulation of membrane antigen. Apart from their primary role as active phagocytes, their involvement in Alzheimer's disease (AD) is evidenced recently by the fact that the cells are specifically marked by antibodies present in the cerebrospinal fluid of AD patients. In conclusion, ramified microglial cells are derived from monocytes, but through an intermediate amoeboid microglia stage as active macrophages in the perinatal period.

The origin and nature of ramified and amoeboid microglia: a historical review and current concepts.

In recent electron microscope studies of the corpus callosum in 60–80 gm male rats, some of the cells were identified as microglia by staining with the weak silver carbonate method of del Rio-Hortega, and others as astrocytes by staining with the gold chloride sublimate method of Ramon y Cajal. In the present work, the cells which did not belong in one of these two groups were examined in the light microscope using semithin sections stained with toluidine blue and in the electron microscope using thin sections stained with uranyl-lead.



These cells make up a large, somewhat heterogeneous group, but they have a few common features: regular nucleus, cytoplasm rich in ribosomes and microtubules, and a variable number of narrow, non-branching fine processes of uniform diameter. Because of these features, the cells are all taken to be oligodendrocytes.



Three classes may be described within this group of cells: (a) light oligodendrocytes, which are large cells with pale nucleus, a large nucleolus, a cytoplasm containing rather small organelles as well as many free ribosomes, and giving off numerous fine processes; they make up about 6% of the glial cells in the corpus callosum; and they undergo mitosis at a rapid rate; (b) medium-shade oligodendrocytes, which are somewhat smaller cells with moderately dense nucleus and cytoplasm, containing well developed organelles, and giving off a fair number of fine processes; they make up about a quarter of the glial cells; and they undergo mitosis at a moderate rate; (c) dark oligodendrocytes, which are even smaller cells with very dense nucleus and cytoplasm, containing a prominent Golgi and structures referred to as lamellar bodies, and giving off very few fine processes; these cells make up about 40% of the glial cells; they do not undergo mitosis and probably arise from divisions of medium oligodendrocytes.

Electron microscopic identification of three classes of oligodendrocytes and a preliminary study of their proliferative activity in the corpus callosum of young rats.

Electron microscopy and 3H-thymidine autoradiographic techniques were used to study the fine structure of proliferating cells in developing rat optic nerve. Before the closure of the optic canal almost all of the cells incorporating radioactive thymidine are ventricular cells, but after closure (16 days of gestation) the vast majority are differentiating astroblasts or oligodendroblasts. Labeled astroblasts show a range in their degree of differentiation; some cells lack 90 A cytoplasmic filaments while others have glial filaments and abundant cytoplasmic organelles. In contrast to astroblasts, all of the labeled oligodendroblasts are in the early stages of differentiation. The proliferation of oligodendroblasts starts at five days postnatal, approximately a day or two before the onset of myelination.During myelinogenesis a few of the labeled oligodendroblasts show presumptive connections to myelin sheaths. Microglial cells do not appear to play a major role in gliogenesis since they form less than 2% of all the labeled cells. The results of this study indicate that astroblasts and oligodendroblasts, rather than undifferentiated glioblasts, are the major source of macroglia. The finding that proliferating glia are in the processof differentiation agrees with recent studies which show that differentiated cells can divide.

Electron microscopic autoradiographic studies of gliogenesis in rat optic nerve I. Cell proliferation

Myelinated nerve fibres in the CNS.

The corpus callosum of 60–80 gm male rats was processed by the weak silver carbonate method of del Rio-Hortega for the detection of microglia in the light microscope. Because of the opacity of the metal stain taken up by these cells, they could be recognized in the electron microscope. The characteristic features of microglia were thus found to be a small nucleus in which dark chromatin contrasts with light nucleoplasm, and a cytoplasm containing dense bodies (presumed to be lysosomes) and poor in endoplasmic reticulum. After gaining experience with microglia in the electron microscope, it became possible to recognize their features in 0.5–1 μ thick toluidine blue stained Epon sections examined in the light microscope.



In the electron microscope, some microglia are found within expansions of the basement membrane of capillaries (pericytal microglia); they usually have little cytoplasm, few dense bodies and few processes. There is evidence that these cells can break out of their basement membrane enclosure and enter the brain tissue proper. There, they scatter singly between other cells and fibers. These cells (interstitial microglia) send of long processes. They may contain numerous dense bodies and be surrounded by irregular spaces (suggesting the existence of surface activity). These observations support the classical view of microglia as brain macrophages.



Microglia constitute 5.5% of the glial population of the corpus callosum. After injection of 3H-thymidine and radioautography in the light or electron microscope, none showed labeling. Hence, it is presumed that microglia do not proliferate under normal conditions.

Identification of microglia in light and electron microscopy

In the prelaminar region of adult cat optic nerve, silver impregnation revealed a macroglial cell population consisting solely of small fibrous astrocytes. Electron microscopically the cells were characterized by abundant processes containing closely packed filaments and occasional glycogen granules; their perikarya contained few organelles, glycogen particles were conspicuous but not abundant, and their cytoplasmic and nucleoplasmic matrices were of low density.



The laminar region contained typical fibrous astrocytes. These cells were characterized by similar processes and matrices but their perikarya contained filaments and were richer in organelles whose orientation was primarily radial.



The postlaminar region contained both astrocytes and oligodendrocytes. The latter were identified as cells characterized by the absence of filaments and glycogen, the presence of canaliculi, dense cytoplasmic and nucleoplasmic matrices and perikarya very rich in organelles, whose orientation was primarily circumferential.



The presence of filaments and/or glycogen on the one hand, and of dense matrices on the other hand, seemed to be mutually exclusive and provided diagnostic criteria for astrocytes and oligodendrocytes respectively. Bivalent forms were not seen. Cells usually identified as microglia were not seen.



The relationship between astrocytes and finely myelinated nerve fibers in the lamina cribrosa indicates a sheath-supporting role. Astrocytes are probably generally concerned with the isolation and insulation of neurons and their processes. Oligodendrocytes may be concerned with the energetic support of neurons and their processes.

The ultrastructural characterization of macroglial cell types

The maturation of neuroglia and of myelin sheaths in the lamina cribrosa and the post-laminar part of the kitten optic nerve have been studied with the electron microscope.

1.

In the post-laminar part of the optic nerve the first appearance of myelin sheaths antedates that of cells on the oligodendrocyte line of development, and is associated with the presence of glioblasts and early astrocytoblasts.




2.

Within the lamina cribrosa the appearance of myelin sheaths is associated with the presence of early and late varieties of astrocytoblast. Glia cells on the oligodendrocyte line of development do not occur in this situation.




3.

It is concluded that the glia cells which form myelin sheaths in kitten optic nerve are early astrocytoblasts.

Gliogenesis and myelination in kitten optic nerve

Glia-nerve fibre relationships in mammalian optic nerve

Previous studies of dehydrogenase systems in normal macroglia cells have yielded conflicting results From investigations including succinic dehydrogenase (SDH), for example, it has variously been reported that only cells with the features of oligodendrocytes showed activity (Friede, 1962), that oligodendrocytes showed more activity than astrocytes (Mossakowski, 1962; Wallace, Volk & Lazarus, 1963), that activity in glial cells was variable, but was of about the same degree in oligodendrocytes and astrocytes (Potanos, Wolf & Cowen, 1959; Rubinstein, Klatzo & Miquel, 1962) and that glial cells showed only a very small amount of activity (Thomas & Pearse, 1961) Friede (1961, 1962), Wallace et al (1963) and Koenig (1964) claimed that most macroglial oxidative metabolism, as demonstrated by their nicotinamine-adenine dinucleotide (NAD) and nicotinamine-adenine dinucleotide phosphate (NADP) tetrazolium reductase (NADTR and NADPTR) content, resides in oligodendrocytes However, Rubinstein et al (1962) found no definite differences in reductase activity between astrocytes and oligodendrocytes, and Thomas & Pearse (1961) found a moderately strong reaction for them only in protoplasmic astrocytes There has been further divergence of opinion in respect of the macroglial distribution of lactic dehydrogenase (LDH) Schiffer & Vesco (1963) emphasized the intense LDH activity of astrocytes in the cerebral cortex However, Wallace et al (1963), Friede, Fleming & Knoller (1963) and Koenig (1964) claimed that oligodendrocytes exhibit high LDH activity By the application of microdissection and microdiver techniques to neuronal perikarya and their satellite cells it has been shown (Hyden, 1962) that glial cells contain proportionately more cytochrome oxidase and SDH than neuronal cell bodies Hamberger (1961) demonstrated that nerve cell bodies mainly utilize glutamate during oxidative metabolism, whereas succinate and pyruvate are essentially oxidized by the glia Hyden (1962), Hamberger & Hyden (1963) and other workers demonstrated enzyme patterns which suggest reciprocal metabolic association between glial cells and neuronal perikarya Unfortunately identification of specific glial cells was not possible in the above studies, though itmay be assumed (Hamberger, 1961) that the admixture of astrocytes with satellite oligodendrocytes did not exceed 10 %

Oxidative enzyme activity in macroglia and axons of cat optic nerve.

Neurone—Satellite Cell Relationship

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

F. Baldwin

Author Tools

Chat about Author