Origin Of Microglia

The origin of ramified microglia has been a longstanding controversial issue, although most authorities would accept that microglia are bone marrow derived and belong to the monocyte/macrophage lineage. The observation that the decline of blood-derived ameboid cells (macrophages) in the CNS during the first postnatal weeks was accompanied by a dramatic increase in the number of ramified micro-glia was suggestive for a transition of ameboid cells into resident ramified microglia. Based on morphological grounds, however, transitional forms between these brain macrophages and resting microglia could not be detected in the developing brain. Moreover, in an attempt to directly address the issue of transition, young mice received bone marrow transplants from transgenic mice, thereby allowing the distinction between host and donor cells in tissues. In these chimeric animals only 10% of parenchymal microglia in the CNS displayed the transgenic signal. In adult animals attempts to directly demonstrate the replacement of ramified parenchymal microglia from bone marrow-derived precursors have so far yielded inconclusive results. Ramified microglia in the adult CNS are an extremely sessile cell population exhibiting virtually no turnover from circulating monocytic precursor cells. In contrast to the parenchymal micro-glia, the perivascular microglia are definitely bone marrow derived and regularly replaced in the adult CNS as demonstrated by use of chimeric rats by Hickey and Kimura.

The view that parenchymal microglia are bone marrow derived has been challenged. Based on their finding that astroglial cultures initiated from newborn mouse neopallium contained bipotential progenitor cells that could give rise to both astrocytes and microglia, Fedoroff and colleagues put forward the idea that parenchymal microglia are of neuroectoder-mal origin, as are all other glia. This view was further supported by the observation that the majority of microglia lacked the transgenic signal after bone marrow transplantation as described previously. Despite the uncertainty about their origin, microglia share most surface molecules with bone marrow-derived monocytes/macrophages.

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