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