ArticleeLife2017
Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Mouse model of atypical DAT deficiency syndrome uncovers dopamine dysfunction associated with parkinsonism and ADHD.The Journal of clinical investigation · 2026Article
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
- Central biogenic amine deficiency with concomitant exploratory behavioral deficits in Dnajc12 knock-out mice.NPJ Parkinson's disease · 2025Article
- Emergent glutamate & dopamine dysfunction in VPS35NPJ Parkinson's disease · 2025Article
- Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.International journal of molecular sciences · 2025Article
- The senescent synapse: A look at autophagy, calcium handling, and mitochondrial bioenergetics at the synapse in ageing and Parkinson's disease.Current research in physiology · 2025Review
- Parkinson's-linked LRRK2-G2019S derails AMPAR trafficking, mobility, and composition in striatum with cell-type and subunit specificity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FOXP1 regulates the development of excitatory synaptic inputs onto striatal neurons and induces phenotypic reversal with reinstatement.Science advances · 2024Article
- Retromer-dependent lysosomal stress in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Parkinson's LRRK2-G2019S risk gene mutation drives sex-specific behavioral and cellular adaptations to chronic variable stress.Frontiers in behavioral neuroscience · 2024Article
- Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain.Acta neuropathologica communications · 2023Article
- Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.Brain research · 2023Article
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- Inhibition of the Exocyst Complex Attenuates the LRRK2 Pathological Effects.International journal of molecular sciences · 2023Article
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Authors and funding
15 authors.
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Abstract
LRRK2 mutations produce end-stage Parkinson's disease (PD) with reduced nigrostriatal dopamine, whereas, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged G2019S mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across a range of ages. Young GKI mice exhibit more vertical exploration, elevated glutamate and dopamine transmission, and aberrant D2-receptor responses. These phenomena decline with age, but are stable in littermates. In young GKI mice, dopamine transients are slower, independent of dopamine transporter (DAT), increasing the lifetime of extracellular dopamine. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI mice. Thus, GKI mice exhibit early, but declining, synaptic and behavioral phenotypes, making them amenable to investigation of early pathophysiological, and later parkinsonian-like, alterations. This model will prove valuable in efforts to develop neuroprotection for PD.
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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.