LRRK2 mutations produce end-stage Parkinson's disease (PD) with reduced nigrostriatal dopamine. Conversely, asymptomatic carriers have increased dopamine turnover and altered brain connectivity. LRRK2 pathophysiology remains unclear, but reduced dopamine and mitochondrial abnormalities occur in aged mutant knock-in (GKI) mice. Conversely, cultured GKI neurons exhibit increased synaptic transmission. We assessed behavior and synaptic glutamate and dopamine function across ages. Young GKI 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, dopamine transients are slower, independent of DAT, increasing dopamine extracellular lifetime. Slowing of dopamine transients is observed with age in littermates, suggesting premature ageing of dopamine synapses in GKI. 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.
Pharmacology, Toxicology and Pharmaceutical Science
2
2%
Other
3
3%
Unknown
35
38%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 October 2017.
All research outputs
#7,586,664
of 28,520,172 outputs
Outputs from eLife
#10,949
of 17,511 outputs
Outputs of similar age
#97,347
of 332,047 outputs
Outputs of similar age from eLife
#257
of 401 outputs
Altmetric has tracked 28,520,172 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 17,511 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 32.1. This one is in the 37th percentile – i.e., 37% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 332,047 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 401 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
