Evidence map›Paper›PMID 25671601›Full record

ArticlePloS one2015

Effects of low doses of pioglitazone on resting-state functional connectivity in conscious rat brain.

Donna G Crenshaw, Karen Asin, William K Gottschalk, Zhifeng Liang, Nanyin Zhang, Allen D Roses

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Where do we stand on fMRI in awake mice?Cerebral cortex (New York, N.Y. : 1991) · 2024
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. 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

6 authors at 2 institutions in 1 country.

Donna G CrenshawZinfandel Pharmaceuticals, Inc., Chapel Hill, NC, United States of America.
Karen AsinTakeda Development Center Americas, Inc., Deerfield, IL, United States of America.
William K GottschalkZinfandel Pharmaceuticals, Inc., Chapel Hill, NC, United States of America.
Zhifeng LiangBiomedical Engineering Department, The Pennsylvania State University, University Park, PA, United States of America.
Nanyin ZhangBiomedical Engineering Department, The Pennsylvania State University, University Park, PA, United States of America.
Allen D RosesZinfandel Pharmaceuticals, Inc., Chapel Hill, NC, United States of America.
Pennsylvania State University · USDeerfield (United States) · US

Funding

Resting-state Neural Networks in Awake RodentsR01NS085200 · NINDS · PENNSYLVANIA STATE UNIVERSITY, THE · PI ZHANG, NANYIN · 2013 to 2024
$3.4M
Longitudinal assessment of trauma on neural circuitry development into adulthoodR01MH098003 · NIMH · PENNSYLVANIA STATE UNIVERSITY, THE · PI KING, JEAN A, ZHANG, NANYIN · 2013 to 2017
$1.8M
NIMH NIH HHS R01 MH098003NIMH NIH HHS R01MH098003NINDS NIH HHS R01 NS085200NINDS NIH HHS R01NS085200
6 · The paper itself

Abstract

Pioglitazone (PIO) is a peroxisome proliferator-activated receptor-γ (PPARγ) agonist in clinical use for treatment of type 2 diabetes (T2DM). Accumulating evidence suggests PPARγ agonists may be useful for treating or delaying the onset of Alzheimer's disease (AD), possibly via actions on mitochondria, and that dose strengths lower than those clinically used for T2DM may be efficacious. Our major objective was to determine if low doses of pioglitazone, administered orally, impacted brain activity. We measured blood-oxygenation-level dependent (BOLD) low-frequency fluctuations in conscious rats to map changes in brain resting-state functional connectivity due to daily, oral dosing with low-dose PIO. The connectivity in two neural circuits exhibited significant changes compared with vehicle after two days of treatment with PIO at 0.08 mg/kg/day. After 7 days of treatment with a range of PIO dose-strengths, connections between 17 pairs of brain regions were significantly affected. Functional connectivity with the CA1 region of the hippocampus, a region that is involved in memory and is affected early in the progression of AD, was specifically investigated in a seed-based analysis. This approach revealed that the spatial pattern of CA1 connectivity was consistent among all dose groups at baseline, prior to treatment with PIO, and in the control group imaged on day 7. Compared to baseline and controls, increased connectivity to CA1 was observed regionally in the hypothalamus and ventral thalamus in all PIO-treated groups, but was least pronounced in the group treated with the highest dose of PIO. These data support our hypothesis that PIO modulates neuronal and/or cerebrovascular function at dose strengths significantly lower than those used to treat T2DM and therefore may be a useful therapy for neurodegenerative diseases including AD.

Indexed as

ConsciousnessAnimalsBody WeightBrainDose-Response Relationship, DrugHippocampusMaleNerve NetPioglitazoneRatsRats, WistarRestThiazolidinedionesPioglitazoneThiazolidinediones

Identifiers

PMID25671601
PMCPMC4324644
OpenAlexW2021350175

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.