ArticleAnnals of clinical and translational neurology2014
LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Long-term oral glucocerebrosidase activator reduces soluble α-synuclein oligomer accumulation in Parkinsonian LRRK2 mutant mouse brain.NPJ Parkinson's disease · 2025Article
- Affective phenotypes in heterozygousFrontiers in genetics · 2025Article
- Loss of mitochondrial CaCell communication and signaling : CCS · 2024Article
- Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.Aging and disease · 2024Review
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- In vivo overexpression of synaptogyrin-3 promotes striatal synaptic dopamine uptake in LRRK2Brain and behavior · 2023Article
- Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.NPJ Parkinson's disease · 2022Article
- The parkinsonian LRRK2 R1441G mutation shows macroautophagy-mitophagy dysregulation concomitant with endoplasmic reticulum stress.Cell biology and toxicology · 2022Article
- Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.NPJ Parkinson's disease · 2022Article
- Homozygous mutation of the LRRK2 ROC domain as a novel genetic model of parkinsonism.Journal of biomedical science · 2022Article
- Transcriptional Regulation of the Synaptic Vesicle Protein Synaptogyrin-3 (International journal of molecular sciences · 2022Article
- LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease.Translational neurodegeneration · 2022Review
- LRRK2, GBA and their interaction in the regulation of autophagy: implications on therapeutics in Parkinson's disease.Translational neurodegeneration · 2022Review
- Article
- Identification of LRRK2 missense variants in the accelerating medicines partnership Parkinson's disease cohort.Human molecular genetics · 2021Article
- Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Bioscience reports · 2020Article
- Article
- LRRK2 and the Endolysosomal System in Parkinson's Disease.Journal of Parkinson's disease · 2020Review
- Progress inFrontiers in neuroscience · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMutations in leucine-rich repeat kinase 2 (LRRK2) pose a significant genetic risk in familial and sporadic Parkinson's disease (PD). R1441 mutation (R1441G/C) in its GTPase domain is found in familial PD. How LRRK2 interacts with synaptic proteins, and its role in dopamine (DA) homeostasis and synaptic vesicle recycling remain unclear.
methodsTo explore the pathogenic effects of LRRK2(R1441G) mutation on nigrostriatal synaptic nerve terminals and locomotor activity, we generated C57BL/6N mice with homozygous LRRK2(R1441G) knockin (KI) mutation, and examined for early changes in nigrostriatal region, striatal synaptosomal [(3)H]-DA uptake and locomotor activity after reserpine-induced DA depletion.
resultsUnder normal conditions, mutant mice showed no differences, (1) in amount and morphology of nigrostriatal DA neurons and neurites, (2) tyrosine hydroxylase (TH), DA uptake transporter (DAT), vesicular monoamine transporter-2 (VMAT2) expression in striatum, (3) COX IV, LC3B, Beclin-1 expression in midbrain, (4) LRRK2 expression in total cell lysate from whole brain, (5) α-synuclein, ubiquitin, and tau protein immunostaining in midbrain, (6) locomotor activity, compared to wild-type controls. However, after a single intraperitoneal reserpine dose, striatal synaptosomes from young 3-month-old mutant mice demonstrated significantly lower DA uptake with impaired locomotor activity and significantly slower recovery from the effects of reserpine.
interpretationAlthough no abnormal phenotype was observed in mutant LRRK2(R1441G) mice, the KI mutation increases vulnerability to reserpine-induced striatal DA depletion and perturbed DA homeostasis resulting in presynaptic dysfunction and locomotor deficits with impaired recovery from reserpine. This subtle nigrostriatal synaptic vulnerability may reflect one of the earliest pathogenic processes in LRRK2-associated PD.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.