UseCases_ArguminSci_Discourse  

PubMed:18634852 JSONTXT 7 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-90 DRI_Outcome denotes Expression of the LRRK2 gene in the midbrain dopaminergic neurons of the substantia nigra.
T2 91-238 DRI_Background denotes A hallmark of Parkinson's disease (PD) is the progressive loss of the A9 midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta.
T3 239-388 DRI_Background denotes Recently, multiple causative mutations have been identified in the leucine-rich repeat kinase 2 (LRRK2) gene for both familial and sporadic PD cases.
T4 389-531 DRI_Background denotes Therefore, to investigate functional roles of LRRK2 in normal and/or diseased brain, it is critical to define LRRK2 expression in mDA neurons.
T5 532-761 DRI_Approach denotes To address whether LRRK2 mRNA and protein are expressed in mDA neurons, we purified DA neurons from the tyrosine hydroxylase (TH)-GFP transgenic mouse using FACS-sorting and analyzed the expression of LRRK2 and other mDA markers.
T6 762-919 DRI_Approach denotes We observed that all mDA markers tested in this study (TH, Pitx3, DAT, Nurr1 and Lmx1a) are robustly expressed only in GFP(+) cells, but not in GFP(-) cells.
T7 920-981 DRI_Background denotes Notably, LRRK2 was expressed in both GFP(+) and GFP(-) cells.
T8 982-1156 DRI_Outcome denotes Consistent with this, our immunohistochemical analyses showed that LRRK2 is expressed in TH-positive mDA neurons as well as in surrounding TH-negative cells in the rat brain.
T9 1157-1336 DRI_Outcome denotes Importantly, in the midbrain region, LRRK2 protein was preferentially expressed in A9 DA neurons of the substantia nigra, compared to A10 DA neurons of the ventral tegmental area.
T10 1337-1418 DRI_Background denotes However, LRRK2 was also highly expressed in the cortical and hippocampal regions.
T11 1419-1643 DRI_Outcome denotes Taken together, our results suggest that LRRK2 may have direct functional role(s) in the neurophysiology of A9 DA neurons and that dysfunction of these neurons by mutant LRRK2 may directly cause their selective degeneration.