Evidence map›Paper›PMID 26947127›Full record

ArticleNeuroscience2016

The p75 neurotrophin receptor augments survival signaling in the striatum of pre-symptomatic Q175(WT/HD) mice.

A B Wehner, A M Milen, R L Albin, B A Pierchala

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

Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.7field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Swedish Nerve Growth Factor Mutation (NGFThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018
    Article
  5. Article
  6. Review
  7. Article
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

4 authors at 1 institution in 1 country.

A B WehnerDepartment of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Neuroscience Graduate Program, University of Michigan School of Medicine, Ann Arbor, MI, USA.
A M MilenDepartment of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
R L AlbinNeuroscience Graduate Program, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
B A PierchalaDepartment of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA; Neuroscience Graduate Program, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address: pierchal@umich.edu.
University of Michigan–Ann Arbor · US

Funding

A p75/Ret Receptor Complex as an Integrator of Survival and DeathR01NS089585 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PIERCHALA, BRIAN ANTHONY · 2015 to 2024
$3.9M
NINDS NIH HHS R01 NS089585
6 · The paper itself

Abstract

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder characterized by a constellation of motor, cognitive, and psychiatric features. Striatal medium spiny neurons, one of the most affected populations, are dependent on brain-derived neurotrophic factor (BDNF) anterogradely transported from the cortex for proper function and survival. Recent studies suggest both receptors for BDNF, TrkB and p75 neurotrophin receptor (p75), are improperly regulated in the striata of HD patients and mouse models of HD. While BDNF-TrkB signaling almost exclusively promotes survival and metabolic function, p75 signaling is able to induce survival or apoptosis depending on the available ligand and associated co-receptor. We investigated the role of p75 in the Q175 knock-in mouse model of HD by examining the levels and activation of downstream signaling molecules, and subsequently examining Hdh(+/Q175);p75(-/-) mice to determine if p75 represents a promising therapeutic target. In Hdh(+/Q175);p75(+/+) mice, we observed enhanced survival signaling as evidenced by an increase in phosphorylation and activation of Akt and the p65 subunit of NFκB in the striatum at 5 months of age and an increase in XIAP expression compared to Hdh(+/+);p75(+/+) mice; this increase was lost in Hdh(+/Q175);p75(-/-) mice. Hdh(+/Q175);p75(-/-) mice also showed a decrease in Bcl-XL expression by immunoblotting compared to Hdh(+/Q175);p75(+/+) and Hdh(+/+);p75(+/+) littermates. Consistent with diminished survival signaling, DARPP-32 expression decreased both by immunoblotting and by immunohistochemistry in Hdh(+/Q175);p75(-/-) mice compared to Hdh(+/+);p75(+/+), Hdh(+/Q175);p75(+/+), and Hdh(+/+);p75(-/-) littermates. Additionally, striatal volume declined to a greater extent in Hdh(+/Q175);p75(-/-) when compared to Hdh(+/Q175);p75(+/+) littermates at 12 months, indicating a more aggressive onset of degeneration. These data suggest that p75 signaling plays an early role in augmenting pro-survival signaling in the striatum and that disruption of p75 signaling at a pre-symptomatic age may exacerbate pathologic changes in Hdh(+/Q175) mice.

Indexed as

Age of OnsetAnimalsbcl-X ProteinCorpus StriatumDisease Models, AnimalDopamine and cAMP-Regulated Phosphoprotein 32FemaleGene Knock-In TechniquesHuntingtin ProteinHuntington DiseaseInhibitor of Apoptosis ProteinsMaleMice, 129 StrainMice, Inbred C57BLMice, TransgenicNerve Tissue ProteinsBcl2l1 protein, mousebcl-X ProteinBirc4 protein, mouseDopamine and cAMP-Regulated Phosphoprotein 32Htt protein, mouseHuntingtin ProteinInhibitor of Apoptosis ProteinsNerve Tissue ProteinsNgfr protein, mouseNuclear ProteinsPpp1r1b protein, mouseProto-Oncogene Proteins c-aktReceptors, Nerve Growth FactorTranscription Factor RelABDNFHuntington’sp75Q175

Identifiers

PMID26947127
PMCPMC4849895
OpenAlexW2288710684

What OpenQuestion holds

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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.