Circadian rhythms of locomotor activity and hippocampal clock genes expression are dampened in vitamin A–deficient rats

Navigatore-Fonzo, Lorena; Delgado, Silvia Marcela; Golini, Rebeca S.; Anzulovich, Ana Cecilia

doi:10.1016/j.nutres.2014.02.002

Cited by 26 publications

(10 citation statements)

References 47 publications

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“…Rhythmic expression of Per2 and Bmal1 was not statistically significant. Rhythmicity of clock gene expression in the hippocampus has, however, been stated by other groups: in rodents (Navigatore-Fonzo et al, 2014) and humans (Li et al, 2013). …”

Section: Discussionmentioning

confidence: 91%

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Christiansen

Bouzinova

Fahrenkrug

et al. 2016

IJNPPY

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Background:Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation of clock gene expression in depressive patients, many studies have reported single-nucleotide polymorphisms in clock genes in these patients.Methods:In the present study we investigated whether a depression-like state in rats is associated with alternations of the diurnal expression of clock genes. The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes: period genes 1 and 2 (Per1 and Per2) and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at a 4h sampling interval within 24h. We quantified expression of clock genes on brain sections in the prefrontal cortex, nucleus accumbens, pineal gland, suprachiasmatic nucleus, substantia nigra, amygdala, ventral tegmental area, subfields of the hippocampus, and the lateral habenula using in situ hybridization histochemistry. Expression of clock genes in the liver was monitored by real-time quantitative polymerase chain reaction (PCR).Results:We found that the effect of CMS on clock gene expression was selective and region specific. Per1 exhibits a robust diurnal rhythm in most regions of interest, whereas Bmal1 and in particular Per2 were susceptible to CMS.Conclusion:The present results suggest that altered expression of investigated clock genes is likely associated with the induction of a depression-like state in the CMS model.

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Section: Discussionmentioning

confidence: 91%

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Christiansen

Bouzinova

Fahrenkrug

et al. 2016

IJNPPY

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“…Previous studies have suggested an important role for vitamin A in circadian rhythms; its deficiency leads to disruption of daily rhythms in locomotor activity and clock gene expression [ 14 – 16 ], as well as reduction of the nocturnal peak in melatonin in the pineal gland and loss of rhythm in MAPK activation [ 26 , 27 ]. The results presented here show that RA, the potent active metabolite of vitamin A, is subject to diurnal changes in production and activity, and it can induce rapid changes in kinase activation in the rat pineal gland.…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence emerging for a new role of RA in the regulation of circadian rhythms (reviewed in Ransom et al [ 13 ]). Vitamin A deficiency (VAD) has been found to disrupt oscillations in clock gene expression [ 14 , 15 ] and daily rhythms of locomotor activity, a direct output of the central circadian clock [ 16 ]. Currently, it is not clear how these effects are mediated, but previous studies have alluded to a role for RA.…”

Section: Introductionmentioning

confidence: 99%

Rhythmic Diurnal Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation

et al. 2018

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Vitamin A is important for the circadian timing system; deficiency disrupts daily rhythms in activity and clock gene expression, and reduces the nocturnal peak in melatonin in the pineal gland. However, it is currently unknown how these effects are mediated. Vitamin A primarily acts via the active metabolite, retinoic acid (RA), a transcriptional regulator with emerging non-genomic activities. We investigated whether RA is subject to diurnal variation in synthesis and signaling in the rat pineal gland. Its involvement in two key molecular rhythms in this gland was also examined: kinase activation and induction of Aanat, which encodes the rhythm-generating melatonin synthetic enzyme. We found diurnal changes in expression of several genes required for RA signaling, including a RA receptor and synthetic enzymes. The RA-responsive gene Cyp26a1 was found to change between day and night, suggesting diurnal changes in RA activity. This corresponded to changes in RA synthesis, suggesting rhythmic production of RA. Long-term RA treatment in vitro upregulated Aanat transcription, while short-term treatment had no effect. RA was also found to rapidly downregulate extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, suggesting a rapid non-genomic action which may be involved in driving the molecular rhythm in ERK1/2 activation in this gland. These results demonstrate that there are diurnal changes in RA synthesis and activity in the rat pineal gland which are partially under circadian control. These may be key to the effects of vitamin A on circadian rhythms, therefore providing insight into the molecular link between this nutrient and the circadian system.

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“…RNA isolation and RT reaction techniques were carried out as described in Navigatore- Fonzo et al (2014). Briefly, total RNA was extracted from hippocampus samples by using the Trizol reagent (Invitrogen Co) as directed by the manufacturers.…”

Section: Rna Isolation and Reverse Transcriptase (Rt) Reactionmentioning

confidence: 99%

“…We and others have demonstrated 24-h patterns of lipid peroxidation and GSH levels in different brain areas. These could be, at least in part, responsible for the circadian oscillation of the cellular redox state (Baydas et al, 2002;Fanjul-Moles et al, 2009;Fonzo et al, 2009;Navigatore Fonzo et al, 2014). Additionally, it has been shown that the circadian system modulates the pathways involved in the production and utilization of GSH (Beaver et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer’s disease

et al. 2017

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The accumulation of amyloid-β (Aβ) peptides in the brain of Alzheimer disease patients is associated to cognitive deficit, increased oxidative stress, and alterations in the circadian rhythms. Brain-derived neurotrophic factor (BDNF) and Neurogranin (RC3), play an important role in the synaptic plasticity underlying memory and learning. Previously, we observed BDNF and RC3 expression follow a daily rhythmic pattern in the hippocampus of young rats. The objective of this study was to investigate the effects of an intracerebroventricular (i.c.v) injection of aggregated Aβ peptide (1-42) on temporal patterns of ApoE protein, Bdnf and Rc3 mRNA, lipid peroxidation (LPO) and reduced glutathione (GSH) levels, in the rat hippocampus. We observed an i.c.v. injection of Aβ aggregates phase shifts daily BDNF and RC3 expression as well as LPO and decreased the mesor of GSH rhythms. ApoE protein levels vary rhythmically throughout the day. ApoE levels increase at ZT 03:39±00:22 in the hippocampus of control rats and at ZT 06:30±00:28 in the treated animals. Thus, elevated levels of Aβ aggregates, characteristic of AD, altered temporal patterns of cognition related-factors, probably, as a consequence of changes in the daily variation of ApoE-mediated Aβ aggregates clearance as well as in the 24h rhythms of the cellular redox state.

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Circadian rhythms of locomotor activity and hippocampal clock genes expression are dampened in vitamin A–deficient rats

Cited by 26 publications

References 47 publications

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Altered Expression Pattern of Clock Genes in a Rat Model of Depression

Rhythmic Diurnal Synthesis and Signaling of Retinoic Acid in the Rat Pineal Gland and Its Action to Rapidly Downregulate ERK Phosphorylation

Daily rhythms of cognition-related factors are modified in an experimental model of Alzheimer’s disease

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