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S Fedoroff

Publications and source records attributed to S Fedoroff.

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Expression of 48-kilodalton intermediate filament-associated protein in differentiating and in mature astrocytes in various regions of the central nervous system.

In this paper we present evidence that the 48-kD intermediate filament-associated protein (IFAP) is expressed relatively late in maturation of astrocytes, after they have acquired the glial fibrillary acidic protein (GFAP). In the astrocytes of white matter in the cerebellum the GFAP is detected at P3, whereas the 48-kD IFAP is detected only at P11. In the periventricular region and the hippocampus the 48-kD IFAP was detected at P6, long after the appearance of GFAP. In adult mice the 48-kD IFAP was observed in GFAP-positive astrocytes in the white matter of cerebellum, spinal cord, brainstem, and corpus callosum as well as in GFAP-positive cells in the grey matter of cerebral cortex and spinal cord. The 48-kD IFAP was not, however, detected in radial glia and their derivatives, in Bergmann glia or in Müller glia. Thus, not all the GFAP-positive astroglia express the 48-kD IFAP. Similarly, 48-kD IFAP was not detected in cells which were GFAP-negative.

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PubMedDate not supplied

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.

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 or 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 astrocyte- 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 C3H/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 and implanted op/op mice and C3H/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.

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