Introduction In mammals the suprachiasmatic nucleus SCN

Introduction In mammals, the suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the master oscillator that controls circadian output [1,2]. The circadian information from environmental light/dark due to  is received via the retinohypothalamic tract, and thus, the phase of the circadian clock adapts to photoperiods [3]. The SCN coordinates the phasing of myriad circadian oscillators that are present in peripheral tissues [4] to ensure that physiology will be temporally coordinated [5–7]. Among mammals, circadian oscillation is driven by a cell autonomous transcription/translation-based negative feedback loop, wherein the transcription factors CLOCK and BMAL1 form functional dimers and induce the expression of negative regulators (Per1, Per2, Per3, Cry1 and Cry2) that regulate their own expression by inhibiting the CLOCK-BMAL1 complex [8]. Generally, the expression of mammalian clock genes oscillate in a robust circadian manner [1,9,10]. Therefore, the oscillation of the clock genes could be a useful marker for defining the phase [11,12] and angle phase of different peripheral clocks. The complex of the transcription factors CLOCK-BMAL1 is also responsible for the activation of various clock-controlled genes (CCGs). Thus, the molecular clockwork controls physiological processes through the regulation of CCGs. The clock-controlled genes represent approximately 10% of the expressed genes in a given tissue, and most of these CCGs are tissue-specific because of the different physiological processes carried out in distinct tissues within the appropriate temporal schedule [13,14]. However, the aberrant or desynchronized expression of clock genes within or among individual tissues may have important consequences for the activation of CCGs and, thus, might lead to organ dysfunction [13,15]. Recent studies have suggested that the genetic or functional disruption of certain clock proteins favors the triggering of senescence [16–18] and various physiological disturbances, such as metabolic syndrome [13, 19–21], carcinogenesis [15, 22–24], and cardiovascular diseases [19]. Thus, the desynchronization of the endogenous clock in relation to the environment or between peripheral tissues might affect homeostasis and circadian rhythms regulation [13,15]. These effects can be seen in shift workers and pilots and flight attendants, who are often subjected to transmeridian flights and suffer from higher incidences of cancer [25–29], metabolic pathologies [30–32] and heart diseases [33–37]. The clock gene Period 3 (Per3) has been shown to be associated with Delayed Sleep Phase Syndrome (DSPS) and human chronotypes [38–40]. In humans, this gene presents a tandem 54-nucleotide motif of four or five copies in its coding region. In Japanese and English subjects, DSPS was associated with the allele of this gene with four copies of the motif [38,39], whereas in Brazil, DSPS is associated with the allele with five copies [40]. Recently, it has been shown that this VNTR (Variable Number in Tandem Repeat) polymorphism may profoundly affect sleeping homeostasis and cognitive performance [41–43]. Recently, new roles of Per3 gene have been proposed in contributing to light input pathways [44] and assisting in timekeeping in the pituitary and lung in mice [45]. Moreover the PER3 VNTR is a special characteristic of primate molecular clock since this genomic region has not been found in any other mammal species. Thus, the objective of this study was to verify whether the expression of the Per3 gene in different tissues occurs in a circadian pattern in capuchin monkeys (Cebus apella), and to determine the phases and the phase relationship between these different tissues. Monkeys are adequate models to study human circadian behavior due to the fact that they exhibit diurnal habits [46] and are genetically closer to humans than rodents and fruit flies [47]. Thus, studies using this animal model may lead to new insights into circadian expression pattern of Per3 in different organs and its relationship with behavior; aiming at the future extrapolation to human health.