Maternal P7C3-A20 Treatment Protects Offspring from Neuropsychiatric Sequelae of Prenatal Stress
| Autor: | Hanna E. Stevens, Alexandra Loren, Rachel Schroeder, Noelle S. Williams, Andrew A. Pieper, Lynn Nguyen, Kavitha Priya Kettimuthu, Edwin Vázquez-Rosa, Coral J. Cintrón-Pérez, Preethy Sridharan |
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| Rok vydání: | 2021 |
| Předmět: |
Interneuron
Physiology Offspring Neurogenesis Clinical Biochemistry Carbazoles Hippocampus Biochemistry Neuroprotection chemistry.chemical_compound Mice P7C3 Pregnancy Forum Original Research Communication medicine Animals Cognitive Dysfunction Molecular Biology General Environmental Science business.industry Embryogenesis Cell Biology medicine.anatomical_structure Neuroprotective Agents chemistry Prenatal stress Prenatal Exposure Delayed Effects General Earth and Planetary Sciences Female NAD+ kinase business Neuroscience Stress Psychological |
| Zdroj: | Antioxid Redox Signal |
| ISSN: | 1557-7716 |
| Popis: | Aims: 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. Results: 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. Innovation: 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. Conclusion: 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. Antioxid. Redox Signal. 35, 511–530. |
| Databáze: | OpenAIRE |
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