Evidence map›Paper›PMID 29859873›Full record

ArticleNeurobiology of disease2018

Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein.

Sudhakar R Subramaniam, Iddo Magen, Nicholas Bove, Chunni Zhu, Vincent Lemesre, Garima Dutta, Chris Jean Elias, Henry A Lester, Marie-Francoise Chesselet

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
1.5field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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  11. Nicotine-Mediated Rescue of α-Synuclein Toxicity Requires Synaptic Vesicle Glycoprotein 2 in Drosophila.Movement disorders : official journal of the Movement Disorder Society · 2023
    Article
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  13. A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
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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

9 authors at 2 institutions in 1 country.

Sudhakar R SubramaniamDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: sudhakar.subramaniam@uci.edu.
Iddo MagenDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nicholas BoveDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Chunni ZhuDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Vincent LemesreDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Garima DuttaDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Chris Jean EliasDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Henry A LesterDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Marie-Francoise ChesseletDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: mchesselet@mednet.ucla.edu.
University of California, Los Angeles · USCalifornia Institute of Technology · US

Funding

Chronic nicotine: cell-specific receptor and circuit alterations in basal gangliaR01AG033954 · NIA · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI LESTER, HENRY A. · 2009 to 2013
$1.7M
NIA NIH HHS R01 AG033954
6 · The paper itself

Abstract

In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic deficits may contribute to these problems, but cholinesterase inhibitors have limited efficacy. Mice over-expressing α-synuclein, a protein critically associated with PD, show deficits in cognitive and social interaction tests, as well as a decrease in cortical acetylcholine. We have evaluated the effects of chronic administration of nicotine in mice over-expressing wild type human α-synuclein under the Thy1-promoter (Thy1-aSyn mice). Nicotine was administered subcutaneously by osmotic minipump for 6 months from 2 to 8 months of age at 0.4 mg/kg/h and 2.0 mg/kg/h. The higher dose was toxic in the Thy1-aSyn mice, but the low dose was well tolerated and both doses ameliorated cognitive impairment in Y-maze performance after 5 months of treatment. In a separate cohort of Thy1-aSyn mice, nicotine was administered at the lower dose for one month beginning at 5 months of age. This treatment partially eliminated the cognitive deficit in novel object recognition and social impairment. In contrast, chronic nicotine did not improve motor deficits after 2, 4 or 6 months of treatment, nor modified α-synuclein aggregation, tyrosine hydroxylase immunostaining, synaptic and dendritic markers, or microglial activation in Thy1-aSyn mice. These results suggest that cognitive and social impairment in synucleinopathies like PD may result from deficits in cholinergic neurotransmission and may benefit from chronic administration of nicotinic agonists.

Indexed as

alpha-SynucleinAnimalsCognition DisordersDrug Administration ScheduleGene ExpressionHumansMiceMice, TransgenicNicotineNicotinic AgonistsSocial Behavior Disordersalpha-SynucleinNicotineNicotinic AgonistsCognitive deficitsMotor deficitsMouse modelNicotineParkinson's diseaseSocial impairmentα-synuclein

Identifiers

PMID29859873
PMCPMC6051902
OpenAlexW2805675505

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.