Journal article
Maternal P7C3-A20 Treatment Protects Offspring from Neuropsychiatric Sequelae of Prenatal Stress
Antioxidants & redox signaling, Vol.35(7), pp.511-530
01/29/2021
DOI: 10.1089/ars.2020.8227
PMCID: PMC8388250
PMID: 33501899
Abstract
Impaired embryonic cortical interneuron development from prenatal stress is linked to adult neuropsychiatric impairment, stemming in part from excessive generation of reactive oxygen species in the developing embryo. Unfortunately, there are no preventive medicines that mitigate the risk of prenatal stress to the embryo, as the underlying pathophysiologic mechanisms are poorly understood. Our goal was to interrogate the molecular basis of prenatal stress-mediated damage to the embryonic brain to identify a neuroprotective strategy.
Chronic prenatal stress in mice dysregulated nicotinamide adenine dinucleotide (NAD
) synthesis enzymes and cortical interneuron development in the embryonic brain, leading to axonal degeneration in the hippocampus, cognitive deficits, and depression-like behavior in adulthood. Offspring were protected from these deleterious effects by concurrent maternal administration of the NAD
-modulating agent P7C3-A20, which crossed the placenta to access the embryonic brain. Prenatal stress also produced axonal degeneration in the adult corpus callosum, which was not prevented by maternal P7C3-A20.
Prenatal stress dysregulates gene expression of NAD
-synthesis machinery and GABAergic interneuron development in the embryonic brain, which is associated with adult cognitive impairment and depression-like behavior. We establish a maternally directed treatment that protects offspring from these effects of prenatal stress.
NAD
-synthesis machinery and GABAergic interneuron development are critical to proper embryonic brain development underlying postnatal neuropsychiatric functioning, and these systems are highly susceptible to prenatal stress. Pharmacologic stabilization of NAD
in the stressed embryonic brain may provide a neuroprotective strategy that preserves normal embryonic development and protects offspring from neuropsychiatric impairment.
Details
- Title: Subtitle
- Maternal P7C3-A20 Treatment Protects Offspring from Neuropsychiatric Sequelae of Prenatal Stress
- Creators
- Rachel Schroeder - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USAPreethy Sridharan - Department of Neuroscience, Case Western Reserve University, Cleveland, Ohio, USALynn Nguyen - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USAAlexandra Loren - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USANoelle S Williams - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USAKavitha P Kettimuthu - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, USACoral J Cintrón-Pérez - Department of Psychiatry and Case Western Reserve University, Cleveland, Ohio, USAEdwin Vázquez-Rosa - Department of Psychiatry and Case Western Reserve University, Cleveland, Ohio, USAAndrew A Pieper - Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University, New York, New York, USAHanna E Stevens - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.35(7), pp.511-530
- DOI
- 10.1089/ars.2020.8227
- PMID
- 33501899
- PMCID
- PMC8388250
- NLM abbreviation
- Antioxid Redox Signal
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Publisher
- United States
- Language
- English
- Date published
- 01/29/2021
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984071983902771
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