Journal
EXPERIMENTAL NEUROLOGY
Volume 275, Issue -, Pages 104-115Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2015.09.001
Keywords
Parkinson's disease; (R1441C) LRRK2; Transgenic mice; Microarray
Categories
Funding
- National Science Council, Taiwan [NSC-96-2314-B-182A-104-MY3, 100-2321-B-182-008, 101-2321-B-182-004, 100-2321-B-182-004, 101-2321-B-182-005, 102-2321-B-182-005, 100-2321-B-182-012, 101-2321-B-182A-001, 102-2321-B-182A-001, 100-2314-B-182A-091-MY3]
- Chang Gung Memorial Hospital [CMRPD1B0332, CMRPG361311, CMRPG381161, CMRPG392001, CMRPG3C1501, CMRPD1C0623, CMRPD1C0693, CMRPG391513, CMRPG300161, EMRP1E1641]
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Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LARK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD. (C) 2015 Elsevier Inc. All rights reserved.
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