Evidence map›Paper›PMID 24657594›Full record

ArticleBehavioural brain research2014

Long-term atorvastatin treatment leads to alterations in behavior, cognition, and hippocampal biochemistry.

Jan M Schilling, Weihua Cui, Joseph C Godoy, Victoria B Risbrough, Ingrid R Niesman, David M Roth, Piyush M Patel, John C Drummond, Hemal H Patel, Alice E Zemljic-Harpf and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Behavioural brain research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

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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

11 authors.

Jan M SchillingVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Weihua CuiDepartment of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Joseph C GodoyVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92092, USA.
Victoria B RisbroughVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92092, USA.
Ingrid R NiesmanDepartment of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA; VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
David M RothVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Piyush M PatelVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
John C DrummondVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Hemal H PatelVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Alice E Zemljic-HarpfVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: azemljicharpf@ucsd.edu.
Brian P HeadVA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA; Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: bhead@ucsd.edu.

Funding

Neuronal-targeted caveolin-1 as a therapy for traumatic brain injuryR01NS073653 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HEAD, BRIAN P · 2012 to 2015
$1.4M
Neuron-Targeted Caveolin-1 as a Therapy for Age-Related NeurodegenerationI01BX001225 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI HEAD, BRIAN P · 2012 to 2014
–
BLRD VA I01 BX001225NINDS NIH HHS NS073653NINDS NIH HHS R01 NS073653
6 · The paper itself

Abstract

Membrane/lipid rafts (MLR) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in the biosynthesis of mevalonic, a precursor to cholesterol via the mevalonate pathway. Because there has been controversy over the effects of statins on neuronal and cognitive function, we investigated the impact of long-term atorvastatin treatment (5mg/kg/d for 7 months by oral gavage) on behavior, cognition, and brain biochemistry in mice. We hypothesized that long-term statin treatment would alter lipid rafts and cognitive function. Atorvastatin treatment resulted in behavioral deficits as measured in paradigms for basic exploration (open field activity) and cognitive function (Barnes maze, startle response) without impairment in global motor function (Rotor Rod). Furthermore, significant changes in MLR-associated proteins (syntaxin-1α and synaptophysin) and a global change of post-synaptic density protein-95 (PSD95) were observed. The observed decreases in the MLR-localized pre-synaptic vesicle proteins syntaxin-1α and synaptophysin suggest a molecular mechanism for the statin-associated impairment of cognitive function that was observed and that has been suggested by the clinical literature.

Indexed as

AnimalsAtorvastatinBehavior, AnimalCognitionDisks Large Homolog 4 ProteinExploratory BehaviorGuanylate KinasesHeptanoic AcidsHippocampusHydroxymethylglutaryl-CoA Reductase InhibitorsMaze LearningMembrane ProteinsMice, Inbred C57BLMotor ActivityPyrrolesReflex, StartleAtorvastatinDisks Large Homolog 4 ProteinDlg4 protein, mouseGuanylate KinasesHeptanoic AcidsHydroxymethylglutaryl-CoA Reductase InhibitorsMembrane ProteinsPyrrolesStx1a protein, mouseSynaptophysinSyntaxin 1Syp protein, mouseAtorvastatinBrainCholesterolHypercholesterolemiaLipidPharmacology

Identifiers

PMID24657594
PMCPMC4059187

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.