Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway

Translational Psychiatry
Peiyan WongX Zhang

Abstract

Pregnenolone sulfate, an endogenous neurosteroid in the central nervous system, is a positive allosteric modulator of the NMDA receptor, and plays a role in the modulation of learning and memory. Here, we study the actions of pregnenolone sulfate using the dopamine transporter knockout (DAT-KO) mice, which exhibit endophenotypes that recapitulate certain symptoms of schizophrenia, including the psychomotor agitation, stereotypy, prepulse inhibition (PPI) deficits and cognitive impairments. We found that acute treatment with pregnenolone sulfate normalized the hyperlocomotion and stereotypic bouts, and rescued the PPI deficits of DAT-KO mice. In addition, long-term treatment with pregnenolone sulfate rescued the cognitive deficits of DAT-KO mice in the novel object recognition and social transmission of food preference tests. We also showed that pregnenolone sulfate normalized behavioral abnormalities in MK801-treated wild-type mice, whereas pregnenolone, its precursor, only partially rescued MK801-induced behavioral abnormalities. This indicates that there are distinct mechanisms of action between pregnenolone sulfate and pregnenolone, and the involvement of NMDA receptor signaling in the action of pregnenolone sulfate. Moreove...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J F FloodE Roberts
Aug 1, 1988·Trends in Neurosciences·D R Weinberger
Jan 1, 1973·The American Journal of Psychiatry·S H Snyder
Jul 1, 1974·The Journal of Clinical Endocrinology and Metabolism·R B BilliarB Little
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·P RobelE E Baulieu
Nov 5, 1997·Endocrinology·N A CompagnoneS H Mellon
Jul 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·M D WangT Bäckström
Jan 14, 1999·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J W NewcomerJ W Olney
Sep 18, 1999·Science·R C Malenka, R A Nicoll
Jan 6, 2001·Neuron·D A Lewis, J A Lieberman
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·A CarlssonM L Carlsson
Sep 21, 2001·The Biochemical Journal·S Frame, P Cohen
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·R R GainetdinovM G Caron
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·M P Scheid, J R Woodgett
Aug 29, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Monique ValléeMichel Le Moal
Jan 28, 2004·Nature Genetics·Effat S EmamianJoseph A Gogos
Mar 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jean-Martin BeaulieuMarc G Caron
Jul 21, 2004·Molecular Psychiatry·P J Harrison, D R Weinberger
Apr 28, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Vladimir M PogorelovWilliam C Wetsel
Feb 9, 2006·Neurobiology of Aging·Patrizia De SarnoRichard S Jope
Feb 24, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kenji HashimotoMasaomi Iyo
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tobias EngelJosé J Lucas
Jun 15, 2006·Cellular and Molecular Neurobiology·Joseph T Coyle
Oct 4, 2006·Neuron·Christopher A RossJoseph T Coyle
Oct 7, 2006·Pharmacology, Biochemistry, and Behavior·Terrell T GibbsDavid H Farb
Nov 25, 2006·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Michael RitsnerAbraham Weizman
Mar 3, 2007·Neuron·Stéphane PeineauGraham L Collingridge
May 23, 2007·Nature Neuroscience·Akira Yoshii, Martha Constantine-Paton
May 26, 2007·Pharmacology & Therapeutics·Gustav AkkSteven Mennerick
Jul 20, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gang LeiKenneth M Johnson
Dec 17, 2008·Current Pharmaceutical Design·Daniela EserRainer Rupprecht
Apr 3, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Christine E MarxLawrence J Shampine
Nov 18, 2009·The American Journal of Psychiatry·Zachary FreybergJonathan A Javitch

❮ Previous
Next ❯

Citations

Jun 9, 2016·Journal of Neurogenetics·Evgeniya V EfimovaTatyana D Sotnikova
Feb 17, 2017·Schizophrenia Research·Željka KoradeChristine Konradi
Aug 3, 2017·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Angélica Salatino-OliveiraMara H Hutz
Oct 16, 2019·Nature Neuroscience·Roberto FrauMiriam Melis
Sep 16, 2020·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·O Yu Fedorenko, S A Ivanova
Feb 20, 2019·Diseases·Satoru MatsudaYasuko Kitagishi
Apr 27, 2019·Frontiers in Endocrinology·Marcia H RatnerDavid H Farb
Jul 28, 2019·Molecular Genetics & Genomic Medicine·Eva Albertsen MaltHilde Loge Nilsen
Dec 19, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Pascal JorrattSaak V Ovsepian
Oct 22, 2017·Neuroscience and Biobehavioral Reviews·Tatiana BarichelloJoao Quevedo
Jun 29, 2018·Pharmacology & Therapeutics·Marina SchvererIsabelle Villey

❮ Previous
Next ❯

Software Mentioned

Image J
TopScan Behaviour Analyzing system
R R Foundation for Statistical Computing

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.