Evidence map›Paper›PMID 28487191›Full record

ArticleNeurobiology of learning and memory2017

Human LRRK2 G2019S mutation represses post-synaptic protein PSD95 and causes cognitive impairment in transgenic mice.

Samuel O Adeosun, Xu Hou, Baoying Zheng, Heather L Melrose, Thomas Mosley, Jun Ming Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of learning and memory, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Affective phenotypes in heterozygousFrontiers in genetics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Samuel O AdeosunDepartment of Pathology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, United States. Electronic address: sadeosun@umc.edu.
Xu HouDepartment of Pathology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, United States. Electronic address: xhou@umc.edu.
Baoying ZhengDepartment of Pathology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, United States. Electronic address: bzheng@umc.edu.
Heather L MelroseDepartment of Neuroscience, Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL 32224, United States. Electronic address: Melrose.heather@mayo.edu.
Thomas MosleyDepartment of Medicine, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, United States. Electronic address: tmosley@umc.edu.
Jun Ming WangDepartment of Pathology, University of Mississippi Medical Center, 2500 N State Street, Jackson, MS 39216, United States. Electronic address: jwang@umc.edu.
Jackson Memorial Hospital · USJacksonville College · US

Funding

Center for Psychiatric NeuroscienceP30GM103328 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI STOCKMEIER, CRAIG ALLEN · 2013 to 2017
$5.5M
Ethanol induced brain injury is decreased by inhibiting TIEG2 mediated cell deathR01AA020103 · NIAAA · UNIVERSITY OF MISSISSIPPI MED CTR · PI WANG, JUNMING · 2011 to 2014
$1.4M
NIAAA NIH HHS R01 AA020103NIGMS NIH HHS P30 GM103328
6 · The paper itself

Abstract

backgroundLRRK2 G2019S mutation is associated with increased kinase activity and is the most common mutation associated with late-onset PD. However, the transgenic mouse model has not recapitulated cardinal PD-related motor phenotypes. Non-motor symptoms of PD including cognitive impairments are very common and may appear earlier than the motor symptoms. The objective of this study was to determine whether human LRRK2 with G2019S mutation causes hippocampus-dependent cognitive deficits in mice.

resultsMale (LRRK2-G2019S) LRRK2-Tg mice showed impairments in the early portion of the Two-day radial arm water maze acquisition trial as well as in the reversal learning on the third day. However, their performance was similar to Non-Tg controls in the probe trial. LRRK2-Tg mice also displayed impairments in the novel arm discrimination test but not in the spontaneous alternation test in Y-maze. Interestingly, there was no statistically significant locomotor impairment during any of these cognitive test, nor in the locomotor tests including open field, accelerating rotarod and pole tests. Expression of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin was lower in hippocampal homogenates of LRRK2-Tg mice.

conclusionConsistent with previous reports in human LRRK2 G2019S carriers, the current data suggests that cognitive dysfunctions are present in LRRK2-Tg mice even in the absence of locomotor impairment. LRRK2 G2019S mutation represses the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. This study also suggests that mild cognitive impairment may appear earlier than motor dysfunctions in LRRK2-G2019S mutation carriers.

Indexed as

AnimalsCognitive DysfunctionDisease Models, AnimalDisks Large Homolog 4 ProteinHippocampusHumansLearningLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMaze LearningMiceMice, TransgenicMotor ActivityMutationReversal LearningDisks Large Homolog 4 ProteinDlg4 protein, mouseLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanCognitive impairmentHippocampusLearning and memoryLRRK2Parkinson’s disease

Identifiers

PMID28487191
PMCPMC5568523
OpenAlexW2611220576

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.