bims-ciryme 2024-09-01 papers

Nat Commun. 2024 Aug 23. 15(1): 7257

Prefrontal cortex molecular clock modulates development of depression-like phenotype and rapid antidepressant response in mice.

David H Sarrazin, Wilf Gardner, Carole Marchese, Martin Balzinger, Chockalingam Ramanathan, Marion Schott, Stanislav Rozov, Maxime Veleanu, Stefan Vestring, Claus Normann, Tomi Rantamäki, Benedicte Antoine, Michel Barrot, Etienne Challet, Patrice Bourgin, Tsvetan Serchov.

Depression is associated with dysregulated circadian rhythms, but the role of intrinsic clocks in mood-controlling brain regions remains poorly understood. We found increased circadian negative loop and decreased positive clock regulators expression in the medial prefrontal cortex (mPFC) of a mouse model of depression, and a subsequent clock countermodulation by the rapid antidepressant ketamine. Selective Bmal1KO in CaMK2a excitatory neurons revealed that the functional mPFC clock is an essential factor for the development of a depression-like phenotype and ketamine effects. Per2 silencing in mPFC produced antidepressant-like effects, while REV-ERB agonism enhanced the depression-like phenotype and suppressed ketamine action. Pharmacological potentiation of clock positive modulator ROR elicited antidepressant-like effects, upregulating plasticity protein Homer1a, synaptic AMPA receptors expression and plasticity-related slow wave activity specifically in the mPFC. Our data demonstrate a critical role for mPFC molecular clock in regulating depression-like behavior and the therapeutic potential of clock pharmacological manipulations influencing glutamatergic-dependent plasticity.

DOI: https://doi.org/10.1038/s41467-024-51716-9

Sci Rep. 2024 08 27. 14(1): 19886

Altered circadian expression of clock genes and clock-regulatory epigenetic modifiers in saliva of children with fetal alcohol spectrum disorders.

Ujjal Das, Jennifer D Thomas, Prashant Tarale, Jackie Soja, Sarah Inkelis, Christina Chambers, Dipak K Sarkar.

Prenatal alcohol-exposed (AE) infants and children often demonstrate disrupted sleep patterns, including more frequent awakenings, reduced total sleep time, and more night-to-night sleep variability. Despite the strong connection between sleep patterns and circadian rhythmicity, relatively little is known about circadian rhythm disruptions in individuals with AE. Recently, several reports demonstrated that evaluating the expression patterns of human clock genes in biological fluids could reveal an individual's circadian phenotype. Human saliva offers an emerging and easily available physiological sample that can be collected non-invasively for core-clock gene transcript analyses. We compared the expression patterns of core-clock genes and their regulatory genes in salivary samples of children aged 6-10 years-old with and without AE during the light cycle between ZT0-ZT11. We isolated the RNA from the samples and measured the expression patterns of core clock genes and clock regulating genes using the human specific primers with quantitative real-time PCR. Analysis of core clock genes expression levels in saliva samples from AE children indicates significantly altered levels in expression of core-clock BMAL1, CLOCK, PER1-3 and CRY1,2, as compared to those in age-matched control children. We did not find any sex difference in levels of clock genes in AE and control groups. Cosinor analysis was used to evaluate the rhythmic pattern of these clock genes, which identified circadian patterns in the levels of core clock genes in the control group but absent in the AE group. The gene expression profile of a salivary circadian biomarker ARRB1 was rhythmic in saliva of control children but was arhythmic in AE children. Altered expression patterns were also observed in clock regulatory genes: NPAS2, NFL3, NR1D1, DEC1, DEC2, and DBP, as well as chromatin modifiers: MLL1, P300, SIRT1, EZH2, HDAC3, and ZR1D1, known to maintain rhythmic expression of core-clock genes. Overall, these findings provide the first evidence that AE disturbs the circadian patten expression of core clock genes and clock-regulatory chromatin modifiers in saliva.

Keywords: Circadian rhythm; Clock genes; Epigenetic; Fetal alcohol spectrum disorders; Salivary transcripts

DOI: https://doi.org/10.1038/s41598-024-71023-z

Proc Biol Sci. 2024 Aug;291(2029): 20240591

Day-night gene expression reveals circadian gene disco as a candidate for diel-niche evolution in moths.

Yash Sondhi, Rebeccah L Messcher, Anthony J Bellantuono, Caroline G Storer, Scott D Cinel, R Keating Godfrey, Andrew J Mongue, Yi-Ming Weng, Deborah Glass, Ryan A St Laurent, Chris A Hamilton, Chandra Earl, Colin J Brislawn, Ian J Kitching, Seth M Bybee, Jamie C Theobald, Akito Y Kawahara.

Temporal ecological niche partitioning is an underappreciated driver of speciation. While insects have long been models for circadian biology, the genes and circuits that allow adaptive changes in diel-niches remain poorly understood. We compared gene expression in closely related day- and night-active non-model wild silk moths, with otherwise similar ecologies. Using an ortholog-based pipeline to compare RNA-Seq patterns across two moth species, we find over 25 pairs of gene orthologs showing differential expression. Notably, the gene disco, involved in circadian control, optic lobe and clock neuron development in Drosophila, shows robust adult circadian mRNA cycling in moth heads. Disco is highly conserved in moths and has additional zinc-finger domains with specific nocturnal and diurnal mutations. We propose disco as a candidate gene for the diversification of temporal diel-niche in moths.

Keywords: Lepidoptera; RNA-Seq; chronobiology; de novo transcriptome; light cycle; temporal

DOI: https://doi.org/10.1098/rspb.2024.0591