Dataset Information

Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life.

ABSTRACT: The circadian clock regulates bodily rhythms by time cues that result from the integration of genetically encoded endogenous rhythms with external cycles, most potently with the light/dark cycle. Chronic exposure to constant light in adulthood disrupts circadian system function and can induce behavioral and physiological arrhythmicity with potential clinical consequences. Since the developing nervous system is particularly vulnerable to experiences during the critical period, we hypothesized that early-life circadian disruption would negatively impact the development of the circadian clock and its adult function. Newborn rats were subjected to a constant light of 16 lux from the day of birth through until postnatal day 20, and then they were housed in conditions of L12 h (16 lux): D12 h (darkness). The circadian period was measured by locomotor activity rhythm at postnatal day 60, and the rhythmic expressions of clock genes and tissue-specific genes were detected in the suprachiasmatic nuclei, retinas, and pineal glands at postnatal days 30 and 90. Our data show that early postnatal exposure to constant light leads to a prolonged endogenous period of locomotor activity rhythm and affects the rhythmic gene expression in all studied brain structures later in life.

SUBMITTER: Kubistova A

PROVIDER: S-EPMC7762254 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life.

Kubištová Aneta A Spišská Veronika V Petrželková Lucie L Hrubcová Leona L Moravcová Simona S Maierová Lenka L Bendová Zdeňka Z

Biomedicines 20201207 12

The circadian clock regulates bodily rhythms by time cues that result from the integration of genetically encoded endogenous rhythms with external cycles, most potently with the light/dark cycle. Chronic exposure to constant light in adulthood disrupts circadian system function and can induce behavioral and physiological arrhythmicity with potential clinical consequences. Since the developing nervous system is particularly vulnerable to experiences during the critical period, we hypothesized tha ...[more]

PMID: 33297440

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Project description:Background:RNA editing is a widespread post-transcriptional modification mechanism in mammalian genomes. Although many editing sites have been identified in domestic pigs (Sus scrofa), little is known about the characteristics and dynamic regulation of RNA editing in the pineal gland (PG), a small neuroendocrine gland that synthesizes and secretes melatonin, which is primarily responsible to modulate sleep patterns. Results:This study analyzed the expression of adenosine-to-inosine (A-to-I) editing regulators and profiled the first dynamic A-to-I RNA editome during postnatal PG development. The results identified ADAR1 as the most abundantly expressed ADAR enzyme, which was down-regulated during postnatal PG development. Furthermore, 47,284 high-confidence RNA editing sites were identified, the majority of which (93.6%) were of the canonical A-to-I editing type, followed by C-to-T editing. Analysis of its characteristics showed that the A-to-I editing sites mostly localized in SINE retrotransposons PRE-1/Pre0_SS. Moreover, a strong deficiency and preference for guanine nucleotides at positions of one base upstream or downstream were found, respectively. The overall editing level at the puberty stage was higher than at both infancy and adulthood stages. Additionally, genome-wide RNA editing was found to exhibit a dynamic stage-specific fashion (postnatally). Genes that underwent developmental changes in RNA editing were associated with catabolic processes as well as protein localization and transport functions, implying that RNA editing might be responsible for the molecular machineries of the postnatal developing PG. Remarkably, RNA editing in 3'-UTRs might regulate gene expression by influencing miRNA binding during PG development. Conclusions:This study profiles the first comprehensive developmental RNA editome in the pig PG, which contributes to the understanding of the importance of post-transcriptionally mediated regulation during mammalian postnatal PG development. Moreover, this study widely extends RNA editome resources in mammals.

Project description:NeuroD1 encodes a basic helix-loop-helix transcription factor involved in the development of neural and endocrine structures. NeuroD1 mRNA is highly abundant in the adult mammalian pineal gland and exhibits a developmental expression pattern similar to the retina. This is consistent with the common evolutionary origin of pinealocytes and retinal photoreceptors. Pinealocytes and retinal photoreceptors express a shared set of phototransduction genes and submammalian pinealocytes are photosensitive. In contrast to the retina, the pineal gland is a relatively homogeneous structure, composed 95% of pinealocytes. This makes the pineal gland a particularly useful model for understanding photoreceptor cell biology. The loss of NeuroD1 in the retina results in progressive photoreceptor degeneration and the molecular mechanisms underlying this retinal degeneration phenotype remain unknown. Similarly, the role that NeuroD1 plays in the pineal gland is unknown. To determine the function of NeuroD1 in the pineal gland and retina, a Cre/loxP recombination strategy was used to selectively target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout (cKO) mice. Tissue specificity was conferred using Cre recombinase expressed under the control of the promoter of Crx, a transcription factor selectively expressed in the pineal gland and retina. Pineal and retinal tissues from two-month-old NeuroD1 cKO and control animals were used in microarray studies to identify candidate genes responsible for the photoreceptor degeneration phenotype. The Cre/loxP recombination strategy was used to target a NeuroD1 floxed allele and generate NeuroD1 conditional knockout mice (NeuroD1floxed::Crx-Cre+/-). NeuroD1 floxed mice (NeuroD1floxed::Crx-Cre-/-) served as the controls. Pineal glands and retinas from two-month-old control and conditional knockout mice were collected at ZT6 and ZT20. 3 pools of 6 pineal glands per genotype and respective time of day were collected for each sample. Similarly, 3 pools of 6 retinas each were also collected. RNA from each pool was extracted and hybridized on the Affymetrix Mouse 430 2.0 array.

Dataset Information

Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life.

Publications

Constant Light in Critical Postnatal Days Affects Circadian Rhythms in Locomotion and Gene Expression in the Suprachiasmatic Nucleus, Retina, and Pineal Gland Later in Life.

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