Phase Differences in Expression of Circadian Clock Genes in the Central Nucleus of the Amygdala, Dentate Gyrus, and Suprachiasmatic Nucleus in the Rat

Harbour, Valerie L.; Weigl, Yuval; Robinson, Barry; Amir, Shimon

doi:10.1371/journal.pone.0103309

Cited by 54 publications

(48 citation statements)

References 25 publications

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“…In the present study, peak expression of PER1 was found at ZT10 and peak expression of PER2 at ZT15 in the SCN, in agreement with results in the mouse [24] and Lewis rats, where peak expression of PER2 occurred in the early part of the dark phase [5]. …”

Section: Discussionsupporting

confidence: 92%

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Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation

Campos

Buchaim

Silva

et al. 2017

Neuroimmunomodulation

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Objective: The clock genes Period (per) 1 and 2 are essential components in the generation and adjustment of biological circadian rhythms by the suprachiasmatic nucleus (SCN). Both genes are also rhythmically present in extrahypothalamic areas such as the hippocampus and cerebellum, considered subordinate oscillators. Several pathological conditions alter rhythmic biological phenomena, but the mechanisms behind these changes involving the clock genes are not well defined. The current study investigated changes in PER1 and PER2 immunoreactivity in the SCN, hippocampus, and cerebellum in a neuroinflammation model. Methods: Wistar rats received lipopolysaccharide (LPS) or vehicle intracerebroventricularly. The melatonin plasmatic content was quantified by ELISA to confirm the alterations in biological rhythms, and PER1 and PER2 immunoreactivities were analyzed in brain sections by immunohistochemistry. Results: In the SCN, intracerebroventricular LPS changed PER1 expression, increasing the number of PER1-immunoreactive (IR) cells at zeitgeber time (ZT) 15, decreasing it at ZT5 and ZT20 and not changing it at ZT10. LPS also induced a decrease in PER2-IR cells at ZT5, ZT10, and ZT15 but not at ZT20 in the SCN. In the hippocampus, LPS induced a decrease in PER1-IR and PER2-IR cells at both ZTs (ZT10 and ZT15). In the cerebellum, LPS increased the number of PER1-IR cells at ZT10 and decreased it at ZT15, while the number of PER2-IR cells was reduced at both ZTs. Conclusions: These results indicate that a neuroinflammatory condition leads to desynchronization of primary and subordinate brain oscillators, supporting the existence of the integration between the immune and the circadian system.

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Section: Discussionsupporting

confidence: 92%

“…The expression of circadian rhythms in physiology and behavior involves the participation of the circadian timing system and includes forebrain structures and the cerebellum [3], subordinate oscillators which, in normal conditions, can express different patterns of clock genes in close phase or in antiphase with the SCN rhythms [4,5]. …”

Section: Introductionmentioning

confidence: 99%

Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation

Campos

Buchaim

Silva

et al. 2017

Neuroimmunomodulation

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“…Generally, we find very high concordance between rhythms in BA11 and BA47. This is interesting because studies in rodents have suggested that there can be differences in phase between adjacent brain regions (36,37).…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Chen

Logan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

238

219

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With aging, significant changes in circadian rhythms occur, including a shift in phase toward a “morning” chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex [Brodmann’s area 11 (BA11) and BA47]. Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression was found in ∼10% of detected transcripts (P < 0.05). Using a metaanalysis across the two brain areas, we identified a core set of 235 genes (q < 0.05) with significant circadian rhythms of expression. These 235 genes showed 92% concordance in the phase of expression between the two areas. In addition to the canonical core circadian genes, a number of other genes were found to exhibit rhythmic expression in the brain. Notably, we identified more than 1,000 genes (1,186 in BA11; 1,591 in BA47) that exhibited age-dependent rhythmicity or alterations in rhythmicity patterns with aging. Interestingly, a set of transcripts gained rhythmicity in older individuals, which may represent a compensatory mechanism due to a loss of canonical clock function. Thus, we confirm that rhythmic gene expression can be reliably measured in human brain and identified for the first time (to our knowledge) significant changes in molecular rhythms with aging that may contribute to altered cognition, sleep, and mood in later life.

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“…For example, there are rhythms of PER2 expression in the forebrain, most of which peak near dawn or dusk [17]. As one indication of the important regional heterogeneity in the mammalian forebrain, a second study by this group showed that the expression of Per2, Bmal1 and Dbp mRNA oscillates, with the phase and amplitude of rhythms of each gene, varying across forebrain regions [18]. Presumably these regional differences ensure that the timing of specific behaviors occur at appropriate times of day.…”

Section: Overview Of the Circadian Timing Systemmentioning

confidence: 99%

Neuroendocrine underpinnings of sex differences in circadian timing systems

Yan

Silver

2016

The Journal of Steroid Biochemistry and Molecular Biology

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There are compelling reasons to study the role of steroids and sex differences in the circadian timing system. A solid history of research demonstrates the ubiquity of circadian changes that impact virtually all behavioral and biological responses. Furthermore, steroid hormones can modulate every attribute of circadian responses including the period, amplitude and phase. Finally, desynchronization of circadian rhythmicity, and either enhancing or damping amplitude of various circadian responses can produce different effects in the sexes. Studies of the neuroendocrine underpinnings of circadian timing systems and underlying sex differences have paralleled the overall development of the field as a whole. Early experimental studies established the ubiquity of circadian rhythms by cataloging daily and seasonal changes in whole organism responses. The next generation of experiments demonstrated that daily changes are not a result of environmental synchronizing cues, and are internally orchestrated, and that these differ in the sexes. This work was followed by the revelation of molecular circadian rhythms within individual cells. At present, there is a proliferation of work on the consequences of these daily oscillations in health and in disease, and awareness that these may differ in the sexes. In the present discourse we describe the paradigms used to examine circadian oscillation, to characterize how these internal timing signals are synchronized to local environmental conditions, and how hormones of gonadal and/or adrenal origin modulate circadian responses. Evidence pointing to endocrinologically and genetically mediated sex differences in circadian timing systems can be seen at many levels of the neuroendocrine and endocrine systems, from the cell, the gland and organ, and to whole animal behavior, including sleep/wake or rest/activity cycles, responses to external stimuli, and responses to drugs. We review evidence indicating that the analysis of the circadian timing system is amenable to experimental analysis at many levels of the neuraxis, and on several different time scales, rendering it especially useful for the exploration of mechanisms associated with sex differences.

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Phase Differences in Expression of Circadian Clock Genes in the Central Nucleus of the Amygdala, Dentate Gyrus, and Suprachiasmatic Nucleus in the Rat

Cited by 54 publications

References 25 publications

Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation

Suprachiasmatic Nucleus and Subordinate Brain Oscillators: Clock Gene Desynchronization by Neuroinflammation

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

Neuroendocrine underpinnings of sex differences in circadian timing systems

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