"Time sweet time": circadian characterization of galectin-1 null mice

Casiraghi, Leandro P.; Croci, Diego O.; Poirier, Françoise; Rabinovich, Gabriel A.; Golombék, Diego A.

doi:10.1186/1740-3391-8-4

Cited by 6 publications

(6 citation statements)

References 44 publications

(43 reference statements)

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“…For example, mice mutant for the Galectin-1 gene, which regulates cytokine synthesis [37], show altered free-running periods and responses to early-night light pulses [38]. Moreover, activation of the immune system can also modulate the circadian clock.…”

Section: Discussionmentioning

confidence: 99%

Characterization of locomotor activity circadian rhythms in athymic nude mice

Paladino¹,

Duhart²,

Fedele³

et al. 2013

J Circadian Rhythms

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BackgroundThe relation between circadian dysregulation and cancer incidence and progression has become a topic of major interest over the last decade. Also, circadian timing has gained attention regarding the use of chronopharmacology-based therapeutics. Given its lack of functional T lymphocytes, due to a failure in thymus development, mice carrying the Foxn1(Δ/Δ) mutation (nude mice) have been traditionally used in studies including implantation of xenogeneic tumors. Since the immune system is able to modulate the circadian clock, we investigated if there were alterations in the circadian system of the athymic mutant mice.MethodsGeneral activity circadian rhythms in 2–4 month-old Foxn1(Δ/Δ) mice (from Swiss Webster background) and their corresponding wild type (WT) controls was recorded. The response of the circadian system to different manipulations (constant darkness, light pulses and shifts in the light–dark schedule) was analyzed.ResultsFree-running periods of athymic mice and their wild type counterpart were 23.86 ± 0.03 and 23.88 ± 0.05 hours, respectively. Both strains showed similar phase delays in response to 10 or 120 minutes light pulses applied in the early subjective night and did not differ in the number of c-Fos-expressing cells in the suprachiasmatic nuclei, after a light pulse at circadian time (CT) 15. Similarly, the two groups showed no significant difference in the time needed for resynchronization after 6-hour delays or advances in the light–dark schedule. The proportion of diurnal activity, phase-angle with the zeitgeber, subjective night duration and other activity patterns were similar between the groups.ConclusionsSince athymic Foxn1(Δ/Δ) mice presented no differences with the WT controls in the response of the circadian system to the experimental manipulations performed in this work, we conclude that they represent a good model in studies that combine xenograft implants with either alteration of the circadian schedules or chronopharmacological approaches to therapeutics.

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Section: Discussionmentioning

confidence: 99%

Characterization of locomotor activity circadian rhythms in athymic nude mice

Paladino¹,

Duhart²,

Fedele³

et al. 2013

J Circadian Rhythms

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“…Comparison of protein abundances (logarithmized L/H ratios) in N2a cells treated with PF-670462 or DMSO showed that the majority (89%, 147 proteins) of differentially expressed proteins were upregulated in response to PF-670462 treatment, with fewer showing downregulation (11%, 19 proteins) (Figure 1B; Table S2). Among these differentially expressed proteins were several proteins previously shown to be involved in circadian regulation and to exhibit diurnal rhythms in expression, including casein kinase 2 (Tsuchiya et al, 2009), prohibitin-2 (Kategaya et al, 2012), calreticulin (Noguchi et al, 2017), and galectin-1 (Casiraghi et al, 2010), suggesting that PF-670462 may exert effects on clock-regulated proteins through CK1δ/ε inhibition. To gain insight into the functions of the set of proteins upregulated in response to PF-670462 treatment (top cluster in Figure 1C), we performed Gene Ontology (GO) enrichment analysis and identified functional terms that were significantly overrepresented compared to a background of the accurately quantified proteins in our dataset.…”

Section: Pf-670462 Treatment Alters Expression Of Ad-related and Clock-regulated Proteins In Vitromentioning

confidence: 99%

Therapeutic Targeting of Casein Kinase 1δ/ε in an Alzheimer’s Disease Mouse Model

et al. 2019

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Sleep disturbances and memory impairment are common symptoms of Alzheimer's disease (AD). Given that the circadian clock regulates sleep, hippocampal function, and neurodegeneration, it represents a therapeutic target against AD. Casein kinase 1δ/ε (CK1δ/ε) are clock regulators and overexpressed in AD brains, making them viable targets to improve sleep and cognition. We assessed the effects of a small molecule CK1δ/ε inhibitor (PF-670462) in a cellular model of circadian clocks and in 3xTg-AD mice. Mass spectrometry-based proteomic analyses revealed that PF-670462 treatment in vitro upregulated multiple proteins that are downregulated in AD, while administration in 3xTg-AD mice reversed hippocampal proteomic alterations in diverse AD-associated and clock-regulated pathways, including synaptic plasticity and amyloid precursor protein processing. Furthermore, PF-670462 rescued working memory and normalized behavioural circadian rhythms in 3xTg-AD mice.Our study provides proof of concept for CK1δ/ε inhibition and direct clock modulation against AD-related proteomic changes, memory impairment, and circadian disturbances.

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“…For example, monocyte chemoattractant protein-1 expression is under the control of BMAL1 in mouse macrophages, and its induction upon a LPS challenge is time dependent (Hayashi et al, 2007;Leone et al, 2012). Also, a circadian phenotype was found in mice KO for the glycan-binding protein galectin-1, suggesting a yet to be defined role in the circadian system (Casiraghi et al, 2010).…”

Section: Effects Of Inflammation and Cytokines On Circadian Rhythmsmentioning

confidence: 99%

Crosstalk between the circadian clock circuitry and the immune system

Cermakian

Lange

Golombék

et al. 2013

Chronobiology International

219

166

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Various features, components, and functions of the immune system present daily variations. Immunocompetent cell counts and cytokine levels present variations according to the time of day and the sleep-wake cycle. Moreover, different immune cell types, such as macrophages, natural killer cells, and lymphocytes, contain a circadian molecular clockwork. The biological clocks intrinsic to immune cells and lymphoid organs, together with inputs from the central pacemaker of the suprachiasmatic nuclei via humoral and neural pathways, regulate the function of cells of the immune system, including their response to signals and their effector functions. Consequences of this include, for example, the daily variation in the response to an immune challenge (e.g., bacterial endotoxin injection) and the circadian control of allergic reactions. The circadian-immune connection is bidirectional, because in addition to this circadian control of immune functions, immune challenges and immune mediators (e.g., cytokines) were shown to have strong effects on circadian rhythms at the molecular, cellular, and behavioral levels. This tight crosstalk between the circadian and immune systems has wide-ranging implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption.

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"Time sweet time": circadian characterization of galectin-1 null mice

Cited by 6 publications

References 44 publications

Characterization of locomotor activity circadian rhythms in athymic nude mice

Characterization of locomotor activity circadian rhythms in athymic nude mice

Therapeutic Targeting of Casein Kinase 1δ/ε in an Alzheimer’s Disease Mouse Model

Crosstalk between the circadian clock circuitry and the immune system

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