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Neurodegeneration and glial activation patterns after mechanical nerve injury are differentially regulated by non‐MHC genes in congenic inbred rat strains
Author(s) -
Lundberg Cecila,
Lidman Olle,
Holmdahl Rickard,
Olsson Tomas,
Piehl Fredrik
Publication year - 2001
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/1096-9861(20010226)431:1<75::aid-cne1056>3.0.co;2-m
Subject(s) - biology , congenic , neurodegeneration , neuroscience , gene , inbred strain , major histocompatibility complex , genetics , disease , pathology , medicine
Ventral root avulsion in the rat leads to a retrograde response, with activation of glia and up‐regulation of immunologic cell surface molecules such as major histocompatibility complex (MHC) antigens, and the subsequent degeneration of a large proportion of the lesioned motoneurons. Herein, we examined several inbred congenic rat strains previously known to react differently to experimentally induced autoimmune diseases and demonstrate a substantial genetic diversity in the regulation of glial activation and neuron death in this injury model. The panel of examined inbred rat strains included DA(RT1AV1), PVG.1AV1, LEW.1AV1, LEW.1N, BN(RT1N) and E3(RT1U), and the following parameters were determined: (1) MHC class II expression on glia; (2) expression of glial fibrillary acidic protein, C3 complement, and microglial response factor‐1 mRNAs in glia; (3) levels of the tumor necrosis factor‐α and interleukin‐1β cytokine mRNAs; (4) degree of motoneuron loss. The findings of considerable strain‐dependent differences in all parameters studied demonstrate important polymorphisms in the genetic regulation of these events. Furthermore, some of the studied features segregated from each other, suggesting independent regulatory mechanisms. Genes outside of the MHC complex are mainly implicated as being of importance for the phenotypic differences, as significant differences were recorded between the MHC congenic strains differing in the non‐MHC genes but not vice versa. These results contribute new important insights into the genetic regulation of glial reactivity and neuron death after mechanical nerve injuries. In addition, the finding of conspicuous strain‐dependent differences makes it necessary to consider the genetic background when designing and interpreting animal experiments involving noxious insults to the central nervous system resulting in glial activation and nerve cell loss. J. Comp. Neurol. 431:75–87, 2001. © 2001 Wiley‐Liss, Inc.