| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-118 |
DRI_Challenge |
denotes |
Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington's disease. |
| T2 |
119-265 |
DRI_Challenge |
denotes |
Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein (Htt). |
| T3 |
266-389 |
DRI_Approach |
denotes |
Group I metabotropic glutamate receptors (mGluRs) are coupled to G(alphaq) and play an important role in neuronal survival. |
| T4 |
390-452 |
DRI_Outcome |
denotes |
We have previously demonstrated that mGluRs interact with Htt. |
| T5 |
453-701 |
DRI_Challenge |
denotes |
Here we used striatal neuronal primary cultures and acute striatal slices to demonstrate that mGluR-mediated signaling pathways are altered in a presymptomatic mouse model of HD (Hdh(Q111/Q111)), as compared to those of control mice (Hdh(Q20/Q20)). |
| T6 |
702-857 |
DRI_Background |
denotes |
mGluR1/5-mediated inositol phosphate (InsP) formation is desensitized in striatal slices from Hdh(Q111/Q111) mice and this desensitization is PKC-mediated. |
| T7 |
858-1015 |
DRI_Background |
denotes |
Despite of decreased InsP formation, (S)-3,5-dihydroxylphenylglycine (DHPG)-mediated Ca(2+) release is higher in Hdh(Q111/Q111) than in Hdh(Q20/Q20) neurons. |
| T8 |
1016-1146 |
DRI_Background |
denotes |
Furthermore, mGluR1/5-stimulated AKT and extracellular signal-regulated kinase (ERK) activation is altered in Hdh(Q111/Q111) mice. |
| T9 |
1147-1242 |
DRI_Background |
denotes |
Basal AKT activation is higher in Hdh(Q111/Q111) neurons and this increase is mGluR5 dependent. |
| T10 |
1243-1360 |
DRI_Outcome |
denotes |
Moreover, mGluR5 activation leads to higher levels of ERK activation in Hdh(Q111/Q111) than in Hdh(Q20/Q20) striatum. |
| T11 |
1361-1539 |
DRI_Background |
denotes |
PKC inhibition not only brings Hdh(Q111/Q111) DHPG-stimulated InsP formation to Hdh(Q20/Q20) levels, but also causes an increase in neuronal cell death in Hdh(Q111/Q111) neurons. |
| T12 |
1540-1731 |
DRI_Challenge |
denotes |
However, PKC inhibition does not modify neuronal cell death in Hdh(Q20/Q20) neurons, suggesting that PKC-mediated desensitization of mGluR1/5 in Hdh(Q111/Q111) mice might be protective in HD. |
| T13 |
1732-1918 |
DRI_Approach |
denotes |
Together, these data indicate that group I mGluR-mediated signaling pathways are altered in HD and that these cell signaling adaptations could be important for striatal neurons survival. |
