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The pregnane xenobiotic receptor, a prominent liver factor, has actions in the midbrain for neurosteroid synthesis and behavioral/neural plasticity of female rats

Overview of attention for article published in Frontiers in Systems Neuroscience, April 2014
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Title
The pregnane xenobiotic receptor, a prominent liver factor, has actions in the midbrain for neurosteroid synthesis and behavioral/neural plasticity of female rats
Published in
Frontiers in Systems Neuroscience, April 2014
DOI 10.3389/fnsys.2014.00060
Pubmed ID
Authors

Cheryl A. Frye, Carolyn J. Koonce, Alicia A. Walf

Abstract

A novel factor of interest for growth/plasticity in the brain is pregnane xenobiotic receptor (PXR). PXR is a liver factor known for its role in xenobiotic clearance and cholesterol metabolism. It is expressed in the brain, suggesting a potential role for plasticity, particularly involving cholesterol-based steroids and neurosteroids. Mating induces synthesis of neurosteroids in the midbrain Ventral Tegmental Area (VTA) of female rodents, as well as other "plastic" regions of the brain, including the hippocampus, that may be involved in the consolidation of the mating experience. Reducing PXR in the VTA attenuates mating-induced biosynthesis of the neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP). The 18 kDA translocator protein (TSPO) is one rate-limiting factor for 3α,5α-THP neurosteroidogenesis. The hypothesis tested was that PXR is an upstream factor of TSPO for neurosteroidogenesis of 3α,5α-THP in the VTA for lordosis, independent of peripheral glands. First, proestrous rats were administered a TSPO blocker (PK11195) and/or 3α,5α-THP following infusions of PXR antisense oligonucleotides (AS-ODNs) or vehicle to the VTA. Inhibiting TSPO with PK11195 reduced 3α,5α-THP levels in the midbrain and lordosis, an effect that could be reversed with 3α,5α-THP administration, but not AS-ODN+3α,5α-THP. Second, proestrous, ovariectomized (OVX), or ovariectomized/adrenalectomized (OVX/ADX) rats were infused with a TSPO enhancer (FGIN 1-27) subsequent to AS-ODNs or vehicle to the VTA. PXR AS-ODNs blocked actions of FGIN 1-27 for lordosis and 3α,5α-THP levels among proestrous > OVX > OVX/ADX rats. Thus, PXR may be upstream of TSPO, involved in neurosteroidogenesis of 3α,5α-THP in the brain for plasticity. This novel finding of a liver factor involved in behavioral/neural plasticity substantiates future studies investigating factors known for their prominent actions in the peripheral organs, such as the liver, for modulating brain function and its augmentation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 12%
Unknown 15 88%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 18%
Student > Ph. D. Student 2 12%
Student > Master 2 12%
Student > Doctoral Student 1 6%
Student > Bachelor 1 6%
Other 3 18%
Unknown 5 29%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 24%
Neuroscience 2 12%
Medicine and Dentistry 2 12%
Psychology 1 6%
Pharmacology, Toxicology and Pharmaceutical Science 1 6%
Other 2 12%
Unknown 5 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 March 2014.
All research outputs
#18,369,403
of 22,751,628 outputs
Outputs from Frontiers in Systems Neuroscience
#1,128
of 1,340 outputs
Outputs of similar age
#163,977
of 226,773 outputs
Outputs of similar age from Frontiers in Systems Neuroscience
#48
of 59 outputs
Altmetric has tracked 22,751,628 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
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