ArticleTranslational psychiatry2015
Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Plasma metabolomics and red blood cell fatty acid profiles in adolescent mental health.Comprehensive psychoneuroendocrinology · 2026Article
- Stable Dopamine-Signaling mRNA Co-Expression in the Substantia Nigra Is Deregulated in Pathological Conditions, but Not in Dopamine Transporter Knockout Rats.Biomolecules · 2025Article
- Childhood insulin resistance and neural stem cell dysfunction in psychiatric disorders: Role ofWorld journal of stem cells · 2025Review
- Molecular basis of neurosteroid and anticonvulsant regulation of TRPM3.Nature structural & molecular biology · 2025Article
- The Ins and Outs of Dopamine Transporter Gene Manipulation: In Vivo Models of DAT Dysfunction.Advances in neurobiology · 2025Review
- Sex-specific maladaptive responses to acute stress upon in utero THC exposure are mediated by dopamine.Pharmacological research · 2024Article
- Article
- Dopamine Transporter Deficient Rodents: Perspectives and Limitations for Neuroscience.Biomolecules · 2023Review
- Temporal effects on death by suicide: empirical evidence and possible molecular correlates.Discover mental health · 2023Article
- A synthetic pregnenolone analog promotes microtubule dynamics and neural development.Cell & bioscience · 2022Article
- A narrative review of treatment interventions to improve cognitive performance in schizophrenia, with an emphasis on at-risk and early course stages.Psychiatry research · 2022Review
- Steroid Sulfation in Neurodegenerative Diseases.Frontiers in molecular biosciences · 2022Review
- Social Interactions of Dat-Het Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy.Biomedicines · 2021Article
- Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update.Current neuropharmacology · 2021Review
- Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone.Nature neuroscience · 2019Article
- Neuropsychiatric phenotype in relation to gene variants in the hemizygous allele in 3q29 deletion carriers: A case series.Molecular genetics & genomic medicine · 2019Article
- Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients.Molecular medicine (Cambridge, Mass.) · 2019Article
- Roles of PI3K/AKT/GSK3 Pathway Involved in Psychiatric Illnesses.Diseases (Basel, Switzerland) · 2019Review
- Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders.Frontiers in endocrinology · 2019Review
- Pronounced Hyperactivity, Cognitive Dysfunctions, and BDNF Dysregulation in Dopamine Transporter Knock-out Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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. Moreover, we found that acute treatment with pregnenolone sulfate increased the phosphorylation levels of striatal AKT and GSK3β in DAT-KO mice, and that long-term treatment with pregnenolone sulfate increased expression levels of NR1 subunit of the NMDA receptor in hippocampus. Thus, pregnenolone sulfate was able to rescue the behavioral anomalies of DAT-KO mice through the NMDA receptor-mediated, AKT/GSK3β signaling pathway.
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