PMID- 35113852
OWN - NLM
STAT- MEDLINE
DCOM- 20220210
LR  - 20240226
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 20
IP  - 2
DP  - 2022 Feb
TI  - A feature of maternal sleep apnea during gestation causes autism-relevant 
      neuronal and behavioral phenotypes in offspring.
PG  - e3001502
LID - 10.1371/journal.pbio.3001502 [doi]
LID - e3001502
AB  - 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.
FAU - Vanderplow, Amanda M
AU  - Vanderplow AM
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Kermath, Bailey A
AU  - Kermath BA
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Bernhardt, Cassandra R
AU  - Bernhardt CR
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Gums, Kimberly T
AU  - Gums KT
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Seablom, Erin N
AU  - Seablom EN
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Radcliff, Abigail B
AU  - Radcliff AB
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Ewald, Andrea C
AU  - Ewald AC
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Jones, Mathew V
AU  - Jones MV
AD  - Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, 
      United States of America.
FAU - Baker, Tracy L
AU  - Baker TL
AUID- ORCID: 0000-0001-9047-3052
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Watters, Jyoti J
AU  - Watters JJ
AUID- ORCID: 0000-0003-1051-506X
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
FAU - Cahill, Michael E
AU  - Cahill ME
AUID- ORCID: 0000-0003-0574-2655
AD  - Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, 
      Wisconsin, United States of America.
LA  - eng
GR  - R01 HL105511/HL/NHLBI NIH HHS/United States
GR  - R01 HL142752/HL/NHLBI NIH HHS/United States
GR  - R25 GM083252/GM/NIGMS NIH HHS/United States
GR  - T32 HD041921/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220203
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autistic Disorder/etiology
MH  - *Behavior, Animal
MH  - Disease Models, Animal
MH  - Female
MH  - Hypoxia/*physiopathology
MH  - Male
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*etiology/physiopathology
MH  - Prosencephalon/growth & development/physiopathology
MH  - Rats, Sprague-Dawley
MH  - Sex Characteristics
MH  - Sleep Apnea Syndromes
MH  - Synapses/*pathology
MH  - TOR Serine-Threonine Kinases
MH  - Rats
PMC - PMC8812875
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/02/04 06:00
MHDA- 2022/02/11 06:00
PMCR- 2022/02/03
CRDT- 2022/02/03 17:17
PHST- 2021/04/13 00:00 [received]
PHST- 2021/11/29 00:00 [accepted]
PHST- 2022/02/03 17:17 [entrez]
PHST- 2022/02/04 06:00 [pubmed]
PHST- 2022/02/11 06:00 [medline]
PHST- 2022/02/03 00:00 [pmc-release]
AID - PBIOLOGY-D-21-00991 [pii]
AID - 10.1371/journal.pbio.3001502 [doi]
PST - epublish
SO  - PLoS Biol. 2022 Feb 3;20(2):e3001502. doi: 10.1371/journal.pbio.3001502. 
      eCollection 2022 Feb.