Neurodegeneration and glial activation patterns after mechanical nerve injury are differentially regulated by non-MHC genes in congenic inbred rat strains

Citation
C. Lundberg et al., Neurodegeneration and glial activation patterns after mechanical nerve injury are differentially regulated by non-MHC genes in congenic inbred rat strains, J COMP NEUR, 431(1), 2001, pp. 75-87
Citations number
52
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF COMPARATIVE NEUROLOGY
ISSN journal
00219967 → ACNP
Volume
431
Issue
1
Year of publication
2001
Pages
75 - 87
Database
ISI
SICI code
0021-9967(20010226)431:1<75:NAGAPA>2.0.ZU;2-M
Abstract
Ventral root avulsion in the rat leads to a retrograde response, with activ ation of glia and up-regulation of immunologic cell surface molecules such as major histocompatibility complex (MHC) antigens, and the subsequent dege neration of a large proportion of the lesioned motoneurons. Herein, we exam ined several inbred congenic rat strains previously known to react differen tly to experimentally induced autoimmune diseases and demonstrate a substan tial genetic diversity in the regulation of glial activation and neuron dea th 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 foll owing parameters were determined: (1) MHC class II expression on glia; (2) expression of glial fibrillary acidic protein, C3 complement, and microglia l response factor-1 mRNAs in glia; (3) levels of the tumor necrosis factor- a and interleukin-lp cytokine mRNAs; (4) degree of motoneuron loss. The fin dings of considerable strain-dependent differences in all parameters studie d demonstrate important polymorphisms in the genetic regulation of these ev ents. Furthermore, some of the studied features segregated from each other, suggesting independent regulatory mechanisms. Genes outside of the MHC com plex are mainly implicated as being of importance for the phenotypic differ ences, as significant differences were recorded between the MHC congenic st rains differing in the non-MHC genes but not vice versa. These results cont ribute new important insights into the genetic regulation of glial reactivi ty and neuron death after mechanical nerve injuries. In addition, the findi ng of conspicuous strain-dependent differences makes it necessary to consid er the genetic background when designing and interpreting animal experiment s involving noxious insults to the central nervous system resulting in glia l activation and nerve cell loss. J. Comp. Neurol. 431:75-87, 2001. (C) 200 1 Wiley-Liss, Inc.