Gestational Chronodisruption Impairs Hippocampal Expression of NMDA Receptor Subunits Grin1b/Grin3a and Spatial Memory in the Adult Offspring
Open accessAbstract
Epidemiological and experimental evidence correlates adverse intrauterine conditions with the onset of disease later in life. For a fetus to achieve a successful transition to extrauterine life, a myriad of temporally integrated humoral/biophysical signals must be accurately provided by the mother. We and others have shown the existence of daily rhythms in the fetus, with peripheral clocks being entrained by maternal cues, such as transplacental melatonin signaling. Among developing tissues, the fetal hippocampus is a key structure for learning and memory processing that may be anticipated as a sensitive target of gestational chronodisruption. Here, we used pregnant rats exposed to constant light treated with or without melatonin as a model of gestational chronodisruption, to investigate effects on the putative fetal hippocampus clock, as well as on adult offspring's rhythms, endocrine and spatial memory outcomes. The hippocampus of fetuses gestated under light:dark photoperiod (12:12 LD) displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock-controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B-3A-3B. In contrast, in the hippocampus of fetuses gestated under constant light (LL), these oscillations were suppressed. In the adult LL offspring (reared in LD during postpartum), we observed complete lack of day/night differences in plasma melatonin and decreased day/night differences in plasma corticosterone. In the adult LL offspring, overall hippocampal day/night difference of gene expression was decreased, which was accompanied by a significant deficit of spatial memory. Notably, maternal melatonin replacement to dams subjected to gestational chronodisruption prevented the effects observed in both, LL fetuses and adult LL offspring. Collectively, the present data point to adverse effects of gestational chronodisruption on long-term cognitive function; raising challenging questions about the consequences of shift work during pregnancy. The present study also supports that developmental plasticity in response to photoperiodic cues may be modulated by maternal melatonin.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Alterations in the rhythms of circadian gene expression are associated with impaired spatial memory in these offspring, and these memory deficits can be prevented by regularly scheduled supplementation of melatonin to the mother.
“Alterations in the rhythms of circadian gene expression are also associated with impaired spatial memory in these offspring46,47, and these memory deficits can be prevented by regularly scheduled supplementation of melatonin to the mother46.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [46]
Rhythms of expression of circadian genes (Bmal1 and Per2) and genes encoding NMDA receptor subunits are suppressed in the hippocampus of adult offspring of rats exposed to constant light during pregnancy.
“Moreover, the rhythms of the expression of circadian genes (specifically, Bmal1 (also known as Arntl) and Per2) and genes encoding NMDA receptor subunits (including Grin1b, Grin3a and Grin3b) are suppressed in the hippocampus of adult offspring of rats exposed to constant light during pregnancy46.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [46]
Hippocampal clock gene rhythms are disrupted after gestation in constant light, and timed infusions of melatonin delivered to the dam prevent these deficits in adult offspring.
“For instance, hippocampal clock gene rhythms are disrupted after gestation in constant light, and timed infusions of melatonin delivered to the dam prevent these deficits in adult offspring15.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
Exposing pregnant mice and rats to constant light produces lasting increases in anxiety-like behavior.
“In previous studies, exposing pregnant mice and rats to constant light produced lasting increases in anxiety-like behavior13–15, with mixed results in learning tasks14–16 and associated hippocampal functions15, 16.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
Exposing pregnant mice and rats to constant light produces mixed results in learning tasks and associated hippocampal functions.
“In previous studies, exposing pregnant mice and rats to constant light produced lasting increases in anxiety-like behavior13–15, with mixed results in learning tasks14–16 and associated hippocampal functions15, 16.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
Perturbed maternal melatonin signaling is a proposed mechanism by which circadian disruption negatively impacts development.
“Previous studies have proposed that perturbed maternal melatonin signaling is a mechanism by which circadian disruption negatively impacts development15, 17, 20–25.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
Other studies have found learning deficits following gestation under constant light.
“Other studies have found learning deficits following gestation under constant light15, 16.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
In these cases, testing was conducted at variable times of day.
“In these cases, testing was conducted at variable times of day.”
From Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice (2017) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 58 · Cited by 86
Research works printed but not linked: 3
- [25]Serón-Ferré M, Mendez N, Abarzua-Catalan L, Vilches N, Valenzuela FJ, et al (2012) Circadian rhythms in the fetus. Molecular and cellular endocrinology 349: 68– 75. 21840372
- [41]Seron-Ferre M, Mendez N, Abarzua-Catalan L, Vilches N, Valenzuela FJ, et al (2012) Circadian rhythms in the fetus. Mol Cell Endocrinol 349: 68– 75. 21840372
- [56]Wang LM, Suthana NA, Chaudhury D, Weaver DR, Colwell CS (2005) Melatonin inhibits hippocampal long-term potentiation. European Journal of Neuroscience 22: 2231– 2237. 16262661 PMC2581482
- Authors
- Vilches, N., Spichiger, C., Mendez, N., Abarzua-Catalan, L., Galdames, H. A., Hazlerigg, D. G., Richter, H. G., & Torres-Farfan, C.
- Affiliations
- Austral University of Chile (CL)
- University of Aberdeen (GB)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-24
- Volume
- 9
- Issue
- 3
- Pages
- e91313
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3963867
- OpenAlex
- W2092406748
- Cited by
- 86
- References
- 58
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 23 · 2019: 10 · 2018: 6 · 2017: 8 · 2016: 2 · 2015: 5 · 2014: 2
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Comisión Nacional de Investigación Científica y Tecnológica
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- hippocampus, NMDA receptor subunits, spatial memory, continuous light exposure, photoperiod, clock genes, Bmal1, Per2, corticosterone, developmental plasticity
- MeSH terms
- Animals, Female, Gene Expression Regulation, Hippocampus, Light, Melatonin, Membrane Glycoproteins, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Photoperiod, Maternal Exposure, Rats, Circadian Clocks, Spatial Memory
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
