Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration

doi:10.1016/0923-2494(92)80090-8

Research in Immunology

Volume 143, Issue 1, 1992, Pages 129-139

https://doi.org/10.1016/0923-2494(92)80090-8 Get rights and content

Summary

We recently reported hyperproduction of interleukin-1 (IL1) and hyperexpression of IL1β mRNA, after in vitro activation by lipopolysaccharide (IPS) in peripheral macrophages of several neurological mutant mice, i.e. staggerer, lurcher, pcd and reeler, that exhibit patterns of neuronal degeneration in the cerebellum; in the present study, we investigated the expression of several cytokine mRNA in peripheral macrophages of other mutants with neuronal degeneration in the cerebellum or in the spinal cord to determine whether this genetic dysregulation is specific for IL1β or whether it reflects a generalized hyperexcitability of these macrophages.

Hyperexpression of IL1β mRNA was present in the cerebellar mutants nodding and nervous, but not in weaver. A similar phenomenon was found, but to a lesser extent, in the spinal mutants dystonia musculorum, wobbler and motor neuron degeneration. On the contrary, no hyperexpression of IL1β mRNA was found in non-genetic models of neuronal degeneration (Wistar rats treated with X irradiation or with 3-acetyl-pyridine).

In the heterozygote staggerer + /sg, which exhibits a late onset of cerebellar neuronal loss, hyperexpression was found not only in 12-month old animals but also in 2-month old ones, i.e. when the number of cerebellar neurons is still normal.

Synthetic molecules (muramyl dipeptides) like MDP or murabutide (Mu), known as macrophage activators, were also efficient in inducing IL1 hyperexpression in sg/sg macrophages. Hyperexpression of two other cytokine mRNA, i.e. IL1α and tumour necrosis factor a mRNA, was also detected in LPS-stimulated macrophages of staggerer and lurcher mutant mice. These data led us to conclude that the macrophages of spinal and cerebellar mutants are in a state of general hyperexcitability.

Work is in progress to establish whether the cytokine abnormalities result from a defect intrinsic to the macrophages of the mutant mice or are secondary to the degenerative process ultimately leading to neuronal loss.

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Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration

Summary

Brain Res. Rev.

Neurosci. Letters

J. Neuroimmunol.

Int. J. Dev. Neurosci.

Brain Res. Rev.

Dev. Brain Res.

Brain Res.

Brain Res.

Bioch. bioph. Res. Commun.

Dev. Brain Res.

Neuroscience

Dev. Brain Res.

Brain Res.

Brain Res.

Neuroscience

The cell biology of macrophage activation

Ann. Rev. Immunol.

Morphological development of the rat cerebellum and some of its mechanisms

Localisation synaptique de l'activité 5′-nucléotidase dans le cortex cerebelleux du rat adulte irradié aux rayons X après la naissance

C.R. Acad. Sci. (Paris)

Cachectin (tumor necrosis factor) : a macrophage hormone governing cellular metabolism and inflammatory response

Endocrine Rev.

A qualitative and quantitative light microscopic study of inferior olivary complex in the adult staggerer mutant mouse

J. Neurogenetics

Structural and quantitative studies on the normal C3H and lurcher mutant mouse

Phil. Trans. roy. Soc. London

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

Biochemistry

Interleukin 1

Rev. infect. Dis.

Clinical relevance of IL-1 and its multiple biological activities

Bull. Inst. Pasteur

Production of prostaglandin E and an interleukin-1-like factor by cultured astrocytes and C6 glioma cells

J. Immunol.

Interleukin 1 stimulation of astroglial proliferation after brain injury

Science

Interleukin 1 of the central nervous system is produced by ameboid microglia

J. exp. Med.