ABSTRACT
Catalepsy is a pathologic behavior which is usually associated with a dysfunction of striatal pallidal pathway and which can be caused by different mechanisms. It was showned previously that hereditary catalepsy is linked with the distal 111.35-116.16 Mb of chromosome 13. We investigated the level of mRNA of 42 genes located in this fragment in two brain regions which are concerned with catalepsy-striatum and substantia nigra in catalepsy-resistant AKR mice strain, in cataleptic CBA mice strain and in congenic cataleptic AKR.CBA-D13Mit76 (D13) mice strain which were created by transferring of this fragment from CBA in AKR genome. We showed congenic D13 mice vary from AKR in level of mRNA of 2 genes (Ndufs4 and Ppap2a genes) in striatum and 10 genes (Esm1, Fst, Gm10735, Gm15322, Gm15323, Gm15324, Gm15325, Il6st, II31ra, Itga1) in sibstantia nigra. The level of mRNA of Mcidas gene is reduced in both brain regions in D13 compared to AKR. Gene expression of Hspb3 n Mocs2, which codes heat shock protein and, molybdenum cofactor synthesis, respectively, in substantia nigra is reduced in cataleptic CBA and D13 mice compared to catalepsy-resistant AKR mice. These genes can be considered as the most likely genes candidate of catalepsy. The revealed genes coexpression shows that there is a difficult genes network, which regulates hereditary catalepsy.
Subject(s)
Catalepsy/genetics , Corpus Striatum/physiology , Gene Expression Regulation , Substantia Nigra/physiology , Animals , Chromosomes , Electron Transport Complex I/genetics , Genetic Predisposition to Disease , Heat-Shock Proteins/genetics , Male , Mice, Inbred AKR , Mice, Inbred CBA , Phosphatidate Phosphatase/genetics , Sulfurtransferases/geneticsABSTRACT
Glycoprotein gp130 is involved in the intracellular transduction of signals from receptors ofinterleukin-6--related cytokines. The linkage between Il6st gene encoding gp130 and predisposition to excessive freezing (catalepsy) in mice was shown. The aim of present study was to investigate the Il6st mRNA concentration, the level and the rate of glycosilation of gp130 in five brain structures in catalepsy-resistant AKR/J mice strain and in catalepsy-prone CBA/LacJ, AKR.CBA-D13Mit76 with the CBA-derived Il6st gene variant in the AKR/J genome, and ASC created by selection of back-crosses between CBA and AKR strains on catalepsy. Highest concentrations of the nonglycosilated and the glycosilated gp130 protein levels were detected in the midbrain. High levels of Il6st mRNA were discovered in the midbrain, the striatum and the hypothalamus in all mouse strains. The level of Il6st mRNA in the striatum of AKR.CBA-D13Mit76 mice was significantly higher compared with AKR/J. An association between hereditary catalepsy and Il6st expression in the striatum in mice was suggested.
Subject(s)
Brain/metabolism , Catalepsy/metabolism , Cytokine Receptor gp130/biosynthesis , Freezing Reaction, Cataleptic , Gene Expression Regulation , Nerve Tissue Proteins/biosynthesis , RNA, Messenger/biosynthesis , Animals , Brain/pathology , Catalepsy/genetics , Catalepsy/pathology , Genetic Predisposition to Disease , Mice , Species SpecificityABSTRACT
Glycoprotein gp130 is involved in signaling out of significant cytokine receptors as interleukin-6 (IL-6), leukemia inhibitory factor and ciliary neurotrophic factor, which play critical role in immunity, inflammation and neurogenesis. IL-6 and brain neurotransmitter serotonin are involved in the mechanism of depression. The aim of this work was to investigat the role of protein gp130 in the regulation of expression of genes, coding the key enzyme of serotonin synthesis--tryptophan hydroxylase 2 (TPH2), 5-HT-transporter, 5-HT(1A)- and 5-HT(2A)-receptors of serotonin. The study was carried out on adult mouse males of AKR and congenic AKR.CBA-D13Mit76 strains, created by transfer of the fragment of chromosome 13 containing the gene coding gp130 protein from CBA/Lac strain to the genome of AKR/J strain. Decreased expression of 5-HT(1A) - 5-HT(2A)-receptor genes in hippocampus midbrain and TPH2 gene in midbrain in AKR.CBA-D13Mit76 mice compared with AKR mice were shown. Activation of nonspecific immunity by bacterial endotoxin lipopolysaccharide (LPS) administration did not affect the genes expression in AKR mice, but increased 5-HT(2A)-receptor expression in midbrain and decreased 5-HT(1A)-receptor expression in cortex in AKR.CBA-D13Mit76 mice. The results indicate: 1) the participation of gp130 in the regulation of TPH2, 5-HT(1A)- and 5-HT(2A)-receptor genes and 2) association of this protein in the genetically determined sensitivity to LPS.
