Premium
The hematopoietic cytokine, colony‐stimulating factor 1, is also a growth factor in the CNS: Congenital absence of CSF‐1 in mice results in abnormal microglial response and increased neuron vulnerability to injury
Author(s) -
Berezovskaya O.,
Maysinger D.,
Fedoroff S.
Publication year - 1995
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/0736-5748(95)00013-7
Subject(s) - microglia , astrocyte , macrophage colony stimulating factor , pathology , neuron , biology , cytokine , neuroglia , medicine , immunology , central nervous system , endocrinology , inflammation , neuroscience , macrophage , biochemistry , in vitro
In this study we used op/op mice, which are deficient in the hematopoietic cytokine, colony‐stimulating factor 1 (CSF‐1), to determine the effect of CSF‐1 on neuronal survival and microglial response in injury. In normal mice microglia express the CSF‐1 receptor and are primarily regulated by CSF‐1, produced mainly by astrocytes. The CSF‐1 deficiency in op/op mice results in a depletion in the number of monocytes and macrophages but does not affect the number of morphology of microglia. We produced an ischemic lesion in the cerebral cortex of mice by disrupting the pia‐arachnoid blood vessels in a defined area. Using Nissl stain and strocyte‐ and microglia‐specific antibodies, we determined the number of viable neurons in such injury and the intensity of glial reaction. The cellular response to injury on the operated side of op/op mice was compared to that on the non‐operated contralateral side and to the cellular response in similar lesions in CSF‐1 producing C 3 H/HeJ mice. We found that the systemic lack of CSF‐1 in op/op mice results in a significant increase in neuron vulnerability to ischemic injury and considerably reduced microglial response to neuron injury. Remedying the CSF‐1 deficiency, either by grafting CSF‐1 secreting astroglia into the brain or by implanting encapsulated CSF‐1 secreting fibroblast‐like cells into the peritoneum, partially restores the microglial response to neuron injury and significantly potentiates neuronal survival in cerebral cortex ischemic lesions. Astroglial reaction was approximately the same in the lesions in op/op mice, grafted annd implanted op/op mice and C 3 H/HeJ mice, indicating that CSF‐1 modulates microglia, but not the response of astrocytes to injury. The degree of neuronal survival was not correlated to the degree of microglial proliferation and intensity of their reaction. We report some indications that CSF‐1, in addition to modulation of microglia, may also act directly on neurons.