Tahereh Tahmasebi,1 Rahim Nosrati,2 Hamed Zare,3 Horieh Saderi,4 Reyhaneh Moradi,1 and One hundred-twenty sweet fruit samples were collected. Iwasaki I, Horie H,Yu TJ, et al. Intracranial teratoma with a prominent rhabdomyogenic element and germinoma in the fourth ventricle. Neurol Med Chir (Tokyo). Iwasaki I, Horie H,Yu TJ,et ranial teratoma with a prominent rhabdomyogenic element and germinoma in the fourth Med Chir (Tokyo).
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Circadian systems represent an endogenous mechanism adapted to cycling environmental conditions. In mammals, the central circadian clock is located in the suprachiasmatic nuclei SCNguiding circadian-regulated biological variables such as the sleep-wake cycle, hormonal secretions and locomotor activity [ 1 ].
Another physiological process that exhibits circadian fluctuations, with obvious implications in disease progression and outcome, is the regulation of immune function.
The link between horeih circadian and the immune systems has been extensively investigated [ 2 – 4 ]. Circadian rhythms within the immune system were described in several tissues and cellular populations [ 5 ].
In humans, the number of lymphocytes and granulocytes peaks during the night, whereas monocytes and neutrophil levels fall during the day [ 6 ].
Major humoral immune responses undergo circadian changes, and rhythms in plasmatic levels of pro-inflammatory cytokines, as well as peptide hormones produced and secreted by immune cells, were horeih reported [ 35 – 7 ]. In addition, circadian outputs might affect the central clock through a feedback mechanism that fine-tunes the system. The influence of the immune over the circadian system has been studied in recent years, and there horihe evidences of the effects of cytokines or chemokines in the central nervous system CNS [ 8 – 13 ].
A growing number of recent evidences point to the existence of a bidirectional interaction swest the immune and circadian systems which might be essential in the study of disease progression and treatment. Moreover, cytokines activate clock genes in CNS glial cells, which could release factors to synchronize CNS neurons [ 16 ]. Galectin-1 Gal1a homodimeric protein of this family, can regulate immune cell homeostasis by modulating cytokine synthesis, T cell survival and dendritic cell physiology reviewed in [ 19 ].
Blockade of Gal1 expression within tumor tissue results in heightened T-cell mediated tumor rejection and increased survival of antitumor Th1 cells [ 20 ]. Recent evidence from our laboratory provided rational explanations for these selective immunosuppressive effects demonstrating the ability of Gal1 to preferentially regulate the survival of particularly glycosylated T-cell subsets [ 21 ] and induce the amplification of tolerogenic signals delivered from dendritic cells to T cells in a paracrine circuit involving IL and IL [ 22 ].
Although the major role for Gal1 has been studied in the context of immune regulation, tumor progression or inflammation [ 1822 – 25 ], recent evidence suggests that it might also play an important role in nerve regeneration [ 26 ], muscle innervation [ 27 ] and neurogenesis [ 2829 ]. In fact, Gal1 is expressed in both motor and sensory neurons [ 30 ] and modifies the expression of neuronal NMDA glutamate receptors [ 31 ]. Galectins have been associated with several biological processes in physiological as well as in pathological conditions reviewed in [ 18 ] ; yet the direct involvement of galectins in animal behavior is largely unexplored.
Based on the evidence that several cytokines and immune factors are known to affect circadian rhythms[ 131432 – 34 ], we wished to explore whether the individual functions of Gal1 displayed on different biological settings, may influence or compromise behavioral parameters.
The experimental protocol was approved by our institutional research committee. At 90 days of age, mice were placed in individual cages provided with a cm running wheel, under a Mice were kept in constant darkness DD in order to characterize the endogenous circadian period.
Time sweet time: circadian characterization of galectin1 null mice
Wheel-running activity was constantly monitored by a digital system Archron, Argentina which recorded the number of wheel revolutions every 5 minutes. Activity phase onset was taken as circadian time 12 CT For reentrainment experiments, animals were initially maintained under a Then, mice were subjected to an abrupt 6-h delay or advance in the phase of the LD cycle by shortening for advances or lengthening for delays the night previous to the shift.
Time for reentrainment to the new LD cycle was defined as the time it took for each animal swedt adjust its activity onset with the new cycle according to the phase angle of the onset on the original LD scheme. Free-running activity periods were determined by Chi-square periodograms.
To analyze alpha the time devoted to nocturnal locomotion and phase angle the difference between activity onset and the time of lights offmean waveforms were obtained from the activity recordings in the free-running interval and the “activity” period alpha was defined as the area of the curve on sweer of the median of activity. The area under the curve was calculated to analyze amplitude and activity concentration; amplitude was defined as the percent of total activity represented swwet the activity period, and concentration of activity was calculated as the ratio of this percent to alpha.
In order to achieve a correct analysis of activity patterns, each individual waveform was built from relative activity data, obtained by determining the ratio of absolute activity counts to average counts in the analyzed period for each animal; this is later referred to as “Relative activity”. Activity onset on each individual day was defined as the first 5-min bin that contained at least 80 wheel revolutions, followed by another bin of at least 80 wheel revolutions within 40 min.
Phase shifts were calculated by measuring the phase difference between eye-fitted regression lines through consecutive activity onset times immediately prior to the light pulse, and at least 10 consecutive activity onset times after the light pulse excluding the 5 cycles immediately after the pulse [ 36 ]. Upon transfer to DD conditions, the endogenous period of wheel-running activity was determined. Significant differences were found between circadian period for both groups; for WT mice, mean period was Both alpha and phase shifts indicated are calculated relative to endogenous free-running period.
Phase angle in LD refers to the difference between the time of lights swet and activity onset negative values indicate animals start running before lights off. P values correspond to Student’s t test. The length of the activity interval i.
Alpha for mutants was In consequence, the amount of activity as related to the total time spent in the activity interval was significantly higher in WT animals as compared to mutants. All data is summarized in Table 1and representative actograms of both groups are shown in Fig. A tendency towards a bimodal pattern in locomotor activity can be seen in mutant mice, although a three-block analysis of alpha revealed no significant differences between groups Fig. Stars indicate day and time of light pulses at CT Clear differences in free-running period and alpha can be appreciated see Table 1.
Moreover, after light pulse at CT 15 i. Time point 0 represents CT Phase delays in response to light pulses at CT15 were significantly larger for mutant mice 2. Data is summarized in Table 1 and representative actograms are shown in Fig. No significant differences were found between the groups for reentrainment to a phase delay or phase advance in the LD cycle. After a 6-h advance of the LD cycle, WT animals took 8. After 6-h delays the corresponding figures were 2.
Low-amplitude phase advances were found for both WT and mutant mice when subjected to light stimulation at CT21, without any significant difference between them data not shown.
According to our results, a deficit in Gal1 expression induces subtle, albeit significant, changes in the circadian behavior of mice. Mutant animals exhibited a longer circadian period and, as expected after this result, a larger phase delay response to light pulses according to the phase response curve of mice; larger phase delays would allow animals with a longer endogenous period to entrain to a h LD cycle.
However, the similarities between reentrainment rate between mutant and WT animals suggest that Gal1 might act on a non-parametric photic mechanism i. In addition, we have preliminary evidence for Gal-1 expression in the suprachiasmatic region of control mice, which was absent in knockout animals see additional File 1: Immunohistochemical analysis of Gal-1 in the suprachiasmatic area.
Indeed, the expression of Gal1 in the suprachiasmatic nuclei SCN region of the CNS would suggest that this factor might be implicated in both the generation and the entrainment of circadian rhythms. It is tempting to speculate that the lack of Gal1 might affect the normal development of SCN neurons, as has been found for other CNS areas such as the olfactory bulb [ 37 – 39 ].
It is possible that small structural differences along neural developmental may elicit changes in the adult circadian behavior and responses to light. Moreover, Gal1 expression in glial cells [ 28294041 ] provides an additional substrate for immune-related effects on circadian responses, since glial cells have been implicated in the generation and modulation of circadian rhythms [ 1642 ].
In particular, astrocytic-derived Gal1 has also been reported to modulate glutamate neurotoxicity by altering the expression of NMDA receptors [ 31 ], which are key actors in the signal transduction pathway for circadian responses to light [ 43 ]. Moreover, changes in these receptors, present in the retinorecipient portion of the SCN and responsive to photic stimulation, might explain at least in part the variation in light-induced phase shifts in the mutants.
The differences reported for circadian period and light-induced phase delays in Gal1 mutants should also be taken into account when employing this model in immune or behavioral research. Further research of daily or circadian fluctuations in specific immune variables should be performed in order to establish the possible implications of Gal1 in the mammalian circadian system.
“Time sweet time”: circadian characterization of galectin-1 null mice
To illustrate this concept, Gal1-mediated tolerogenic mechanisms, including promotion of T cell apoptosis, modulation of Th2 cytokine balance or the control of dendritic cell physiology may be selectively influenced by the circadian system.
This implies caution in the monitoring of these immunoregulatory effects which may substantially fluctuate during the light-dark cycle. In conclusion, we provide the first evidence of alterations in the behavior of mice devoid of Gal1, which prompts further investigation of the relevance of this endogenous protein in physiopathological processes.
All authors approved the final version of the manuscript. Immunohistochemical analysis of Galectin-1 in the suprachiasmatic area. Samples were then incubated with anti-Gal1 rabbit polyclonal IgG 1: Following extensive washing, samples were mounted in anti-fading solution on glass slides and analyzed on a Nikon E scanning laser confocal microscope. As a control, primary antibody was omitted in some sections and processed as described above.
Cellular nuclei were stained with propidium iodine. To determine whether Gal1 plays a role in the regulation of mice circadian behavior, we evaluated expression of this glycan-binding protein in the suprachiasmatic region of the brain. In the pictures, propidium iodine-stained nuclei are shown in red and Gal-1 expression is stained in green.
Isolation of indigenous Glutathione producing Saccharomyces cerevisiae strains
In addition, strong gal-1 expression was found in the olfactory bulb of wild-type mice data not shown. Proc Soc Exp Biol Med Pathophysiological interactions between the circadian and the immune systems. Langenbecks Arch Surg G-CSF as a quality of life improving factor.
Eur Surg Res J Mol Neurosci Nava, F; Carta, G; Haynes, LW Lipopolysaccharide increases arginine-vasopressin release from rat suprachiasmatic nucleus slice cultures. J Neurosci Res Expert Rev Mol Med Nat Rev Immunol 9: Liu, FT Regulatory roles of galectins in the immune response. Int Arch Allergy Immunol Nat Rev Cancer 5: Svensson, A; Tagerud, S Galectin-1 expression in innervated and denervated skeletal muscle. Cell Mol Biol Lett Curr Drug Targets 6: Eur J Neurosci J Biol Rhythms Edelstein, K; de la Iglesia, HO; Schwartz, WJ; Mrosovsky, N Behavioral arousal blocks light-induced phase advances in locomotor rhythmicity but not light-induced Per1 and Fos expression in the hamster suprachiasmatic nucleus.
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