A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring

Autor: Amanda M. Vanderplow, Bailey A. Kermath, Cassandra R. Bernhardt, Kimberly T. Gums, Erin N. Seablom, Abigail B. Radcliff, Andrea C. Ewald, Mathew V. Jones, Tracy L. Baker, Jyoti J. Watters, Michael E. Cahill
Rok vydání: 2021
Předmět:
Male
Maternal Health
Social Sciences
Rats
Sprague-Dawley
Cognition
Learning and Memory
Pregnancy
Animal Cells
Medicine and Health Sciences
Psychology
Biology (General)
Hypoxia
Neurons
Mammals
Sex Characteristics
Behavior
Animal
Animal Behavior
General Neuroscience
TOR Serine-Threonine Kinases
Eukaryota
Obstetrics and Gynecology
Animal Models
Chemistry
Experimental Organism Systems
Prenatal Exposure Delayed Effects
Animal Sociality
Vertebrates
Physical Sciences
Female
Cellular Types
General Agricultural and Biological Sciences
Research Article
Chemical Elements
QH301-705.5
Research and Analysis Methods
Rodents
General Biochemistry
Genetics and Molecular Biology
Prosencephalon
Sleep Apnea Syndromes
Model Organisms
Memory
Animals
Autistic Disorder
Behavior
General Immunology and Microbiology
Organisms
Cognitive Psychology
Biology and Life Sciences
Cell Biology
Neuronal Dendrites
Rats
Oxygen
Disease Models
Animal
Cellular Neuroscience
Synapses
Amniotes
Animal Studies
Women's Health
Cognitive Science
Perception
Visual Object Recognition
Zoology
Neuroscience
Zdroj: PLoS Biology
PLoS Biology, Vol 20, Iss 2, p e3001502 (2022)
ISSN: 1545-7885
Popis: Mounting epidemiologic and scientific evidence indicates that many psychiatric disorders originate from a complex interplay between genetics and early life experiences, particularly in the womb. Despite decades of research, our understanding of the precise prenatal and perinatal experiences that increase susceptibility to neurodevelopmental disorders remains incomplete. Sleep apnea (SA) is increasingly common during pregnancy and is characterized by recurrent partial or complete cessations in breathing during sleep. SA causes pathological drops in blood oxygen levels (intermittent hypoxia, IH), often hundreds of times each night. Although SA is known to cause adverse pregnancy and neonatal outcomes, the long-term consequences of maternal SA during pregnancy on brain-based behavioral outcomes and associated neuronal functioning in the offspring remain unknown. We developed a rat model of maternal SA during pregnancy by exposing dams to IH, a hallmark feature of SA, during gestational days 10 to 21 and investigated the consequences on the offspring’s forebrain synaptic structure, synaptic function, and behavioral phenotypes across multiples stages of development. Our findings represent a rare example of prenatal factors causing sexually dimorphic behavioral phenotypes associated with excessive (rather than reduced) synapse numbers and implicate hyperactivity of the mammalian target of rapamycin (mTOR) pathway in contributing to the behavioral aberrations. These findings have implications for neuropsychiatric disorders typified by superfluous synapse maintenance that are believed to result, at least in part, from largely unknown insults to the maternal environment.
Correlative data in humans has hinted at an association between maternal sleep apnea during pregnancy and altered neuronal function in offspring. This study shows that in a rat model of sleep apnea, maternal gestational intermittent hypoxia leads to sex-specific changes in neuronal structure and function in offspring, accompanied by impaired behavioral phenotypes.
Databáze: OpenAIRE
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