Evidence map›Paper›PMID 27031732›Full record

ArticleJournal of Huntington's disease2016

Partial Amelioration of Peripheral and Central Symptoms of Huntington's Disease via Modulation of Lipid Metabolism.

Jane Y Chen, Conny Tran, Lin Hwang, Gang Deng, Michael E Jung, Kym F Faull, Michael S Levine, Carlos Cepeda

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

Article in Journal of Huntington's disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

23 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  10. Potential mechanisms to modify impaired glucose metabolism in neurodegenerative disorders.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Review
  11. Review
  12. Article
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  14. Neuroimmunometabolism: A New Pathological Nexus Underlying Neurodegenerative Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Review
  15. Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022
    Review
  16. Article
  17. Review
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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

8 authors at 2 institutions in 1 country.

Jane Y ChenIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Conny TranIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Lin HwangPasarow Mass Spectrometry Laboratory, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Gang DengDepartment of Chemistry and Biochemistry, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Michael E JungDepartment of Chemistry and Biochemistry, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Kym F FaullPasarow Mass Spectrometry Laboratory, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Michael S LevineIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
Carlos CepedaIntellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, CA, USA.
University of California, Los Angeles · USIntel (United States) · US

Funding

UCLA MSD ProgramR25GM055052 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BARBER, PAUL HENRY, HASSON, TAMA W. · 1996 to 2021
$9.2M
Transgenic Mouse Models of Huntington's DiseaseR01NS041574 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LEVINE, MICHAEL S. · 2002 to 2016
$5.4M
Modulation of Lipid Metabolism to Rescue Aberrant Synaptic Transmission in HDR21NS081335 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CEPEDA, CARLOS T · 2012 to 2013
$417k
NIGMS NIH HHS R25 GM055052NINDS NIH HHS NS081335NINDS NIH HHS NS41574NINDS NIH HHS R01 NS041574NINDS NIH HHS R21 NS081335
6 · The paper itself

Abstract

backgroundHuntington's disease (HD) is a fatal, inherited neurodegenerative disorder characterized by uncontrollable dance-like movements, as well as cognitive deficits and mood changes. A feature of HD is a metabolic disturbance that precedes neurological symptoms. In addition, brain cholesterol synthesis is significantly reduced, which could hamper synaptic transmission.

objectiveAlterations in lipid metabolism as a potential target for therapeutic intervention in the R6/2 mouse model of HD were examined.

methodsElectrophysiological recordings in vitro examined the acute effects of cholesterol-modifying drugs. In addition, behavioral testing, effects on synaptic activity, and measurements of circulating and brain tissue concentrations of cholesterol and the ketone β-hydroxybutyrate (BHB), were examined in symptomatic R6/2 mice and littermate controls raised on normal chow or a ketogenic diet (KD).

resultsWhole-cell voltage clamp recordings of striatal medium-sized spiny neurons (MSNs) from symptomatic R6/2 mice showed increased frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) compared with littermate controls. Incubation of slices in cholesterol reduced the frequency of large-amplitude sIPSCs. Addition of BHB or the Liver X Receptor (LXR) agonist T0901317 reduced the frequency and amplitude of sIPSCs. Surprisingly, incubation in simvastatin to reduce cholesterol levels also decreased the frequency of sIPSCs. HD mice fed the KD lost weight more gradually, performed better in an open field, had fewer stereotypies and lower brain levels of cholesterol than mice fed a regular diet.

conclusionsLipid metabolism represents a potential target for therapeutic intervention in HD. Modifying cholesterol or ketone levels acutely in the brain can partially rescue synaptic alterations, and the KD can prevent weight loss and improve some behavioral abnormalities.

Indexed as

Diet, Ketogenic3-Hydroxybutyric AcidAnimalsCholesterolFemaleHuntington DiseaseInhibitory Postsynaptic PotentialsLipid MetabolismMaleMicePatch-Clamp TechniquesSimvastatinWeight Loss3-Hydroxybutyric AcidCholesterolSimvastatincholesterolelectrophysiologyketogenic dietR6/2 modelsynaptic activity

Identifiers

PMID27031732
PMCPMC5002395
OpenAlexW2313927773

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.