| First Author | Bakalian A | Year | 1992 |
| Journal | Res Immunol | Volume | 143 |
| Issue | 1 | Pages | 129-39 |
| PubMed ID | 1565842 | Mgi Jnum | J:2228 |
| Mgi Id | MGI:50752 | Doi | 10.1016/0923-2494(92)80090-8 |
| Citation | Bakalian A, et al. (1992) Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration. Res Immunol 143(1):129-39 |
| abstractText | We recently reported hyperproduction of interleukin-1 (IL1) and hyperexpression of IL1 beta mRNA, after in vitro activation by lipopolysaccharide (LPS) 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 IL1 beta or whether it reflects a generalized hyperexcitability of these macrophages. Hyperexpression of IL1 beta 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 IL1 beta 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. IL1 alpha and tumour necrosis factor alpha 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. |
