Papers by Lisandro Lungato
Background: Sleep is a physiological event that directly influences health by affecting the immun... more Background: Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca 2+ ) plays a critical signaling role. We performed live cell measurements of cytosolic Ca 2+ mobilization to understand the changes in Ca 2+ signaling that occur in splenic immune cells after various periods of sleep deprivation (SD). Methods: Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72 h) and Ca 2+ intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca 2+ mobilization in endoplasmic reticulum and mitochondria. Additionally, Ca 2+ channel gene expression was evaluated Results: Splenocytes showed a progressive loss of intracellular Ca 2+ maintenance from endoplasmic reticulum (ER) stores. Transient Ca 2+ buffering by the mitochondria was further compromised. These findings were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca 2+ channels. Conclusions and general significance: These novel data suggest that SD impairs Ca 2+ signaling, most likely as a result of ER stress, leading to an insufficient Ca 2+ supply for signaling events. Our results support the previously described immunosuppressive effects of sleep loss and provide additional information on the cellular and molecular mechanisms involved in sleep function.
Objectives: Chitotriosidase (CHIT) is a functional chitinase
secreted by activated macrophages. C... more Objectives: Chitotriosidase (CHIT) is a functional chitinase
secreted by activated macrophages. Considering that sleep is an
important physiological event that directly influences health and is
related to immune system function, our aim is to verify whether the
activity of CHIT is altered after paradoxical sleep deprivation (PSD)
and to assess the extent to which recovery sleep could affect this
biological process. Methods: We analyzed CHIT enzymatic activity
of Swiss and C57BL/6 mice and Wistar rats submitted to PSD for
72 hours without sleep rebound and with 24 hours of free sleep
following PSD. Results: We observed an increase in the activity of
plasma CHIT in PSD Swiss mice when compared to the Control
group (CT) (p < 0.05), C57BL/6 mice (p < 0.05) and Wistar rats
(p < 0.05). After 24 hours of sleep, no differences were observed
in rebound group (RG) compared to PSD Swiss mice (p > 0.05).
Moreover, differences were significant among RG C57BL/6 mice
(p < 0.05) and RG Wistar rats (p < 0.01) compared with their
respective PSD groups. Conclusions: Our data suggest that
CHIT is a relevant marker of macrophage activation, not only for
infections and diseases but also after 72h of PSD in mice and rats.
Background: Sleep is a physiological event that directly influences health by affecting the immun... more Background: Sleep is a physiological event that directly influences health by affecting the immune system, in
which calcium (Ca2+) plays a critical signaling role. We performed live cell measurements of cytosolic Ca2+
mobilization to understand the changes in Ca2+ signaling that occur in splenic immune cells after various
periods of sleep deprivation (SD).
Methods: Adult male mice were subjected to sleep deprivation by platform technique for different periods
(from 12 to 72 h) and Ca2+ intracellular fluctuations were evaluated in splenocytes by confocal microscopy.
We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca2+ mobilization in
endoplasmic reticulum and mitochondria. Additionally, Ca2+ channel gene expression was evaluated
Results: Splenocytes showed a progressive loss of intracellular Ca2+ maintenance from endoplasmic reticulum
(ER) stores. Transient Ca2+ buffering by the mitochondria was further compromised. These findings
were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium
entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca2+ channels.
Conclusions and general significance: These novel data suggest that SD impairs Ca2+ signaling, most likely as a
result of ER stress, leading to an insufficient Ca2+ supply for signaling events. Our results support the previously
described immunosuppressive effects of sleep loss and provide additional information on the cellular
and molecular mechanisms involved in sleep function.
Effects of Sleep Deprivation on Mice Bone Marrow and Spleen B Lymphopoiesis
Journal of Cellular Physiology, 2015
B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response.... more B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response. Sleep is an essential event for the maintenance and integrity of all systems, including the immune system (IS). Thus, sleep deprivation (SD) causes problems in metabolism and homeostasis in many cell systems, including the IS. In this study, our goal was to determine changes in B lymphocytes from the bone marrow (BM) and spleen after SD. Three-month-old male Swiss mice were used. These mice were sleep deprived through the modified multiple platform method for different periods (24, 48, and 72 h), whereas another group was allowed to sleep for 24 h after 72 h of SD (rebound group) and a third group was allowed to sleep normally during the entire experiment. After this, the spleen and BM were collected, and cell analyses were performed. The numbers of B lymphocytes in the BM and spleen were reduced by SD. Additionally, reductions in the percentage of lymphocyte progenitors and their ability to form colonies were observed. Moreover, an increase in the death of B lymphocytes from the BM and spleen was associated with an increase in oxidative stress indicators, such as DCFH-DA, CAT and mitochondrial SOD. Rebound was not able to reverse most of the alterations elicited by SD. The reduction in B lymphocytes and their progenitors by cell death, with a concomitant increase in oxidative stress, showed that SD promoted a failure in B lymphopoiesis. This article is protected by copyright. All rights reserved.
052 QUANTITATIVE ANALYSIS OF PRESENILIN-1 EXPRESSION IN HIPPOCAMPI OF MICE SUBMITTED TO SLEEP DEPRIVATION
Sleep Medicine, 2009
Malaria Journal, 2015
Background: Parasitic diseases like malaria are a major public health problem in many countries a... more Background: Parasitic diseases like malaria are a major public health problem in many countries and disrupted sleep patterns are an increasingly common part of modern life. The aim of this study was to assess the effects of paradoxical sleep deprivation (PSD) and sleep rebound (RB) on malarial parasite infection in mice. Methods: After PSD, one group was immediately infected with parasites (PSD). The two other PSD rebound groups were allowed to sleep normally for either 24 h (24 h RB) or 48 h (48 h RB). After the recovery periods, mice were inoculated with parasites. Results: The PSD group was the most affected by parasites presenting the higher death rate (0.02), higher number of infected cells (p < 0.01), and decrease in body weight (p < 0.04) compared to control and 48 h RB groups. The 24 h RB group was also different from control group in survival (p < 0.03), number of infected cells (p < 0.05) and body weight (p < 0.04). After 48 hours of sleep rebound animals were allowed to restore their response to parasitic infection similar to normal sleep animals. Conclusions: These results suggest that PSD is damaging to the immune system and leads to an increased infection severity of malaria parasites; only 48 hours of recovery sleep was sufficient to return the mice infection response to baseline values.
Stem cells (Dayton, Ohio), 2014
There are a growing number of reports showing the influence of redox modulation in cellular signa... more There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, Ca...
211 SLEEP DEPRIVATION ALTERS LIVER GLYCOGEN CONCENTRATIONS IN MALE MICE
Sleep Medicine, 2009
203 SPLEEN CELLULARITY IS ALTERED BY PARADOXAL SLEEP DEPRIVATION
Sleep Medicine, 2009
Journal of Leukocyte Biology, 2011
Tocopherols promote or inhibit growth in different cell types. In the hematopoietic system, the r... more Tocopherols promote or inhibit growth in different cell types. In the hematopoietic system, the radioprotective property of tocopherols is thought to act through the expansion of primitive hematopoietic cells. However, the mechanisms activated by tocopherols and which HPs are affected remain poorly understood. To better address these questions, mice were treated with ␣-tocopherol, and its effects were investigated in the BM microenvironment. ␣-Tocopherol induced increased proliferation in HSC/HP cells, leading to BM hyperplasia. In addition, differentiation to the granulocytic/monocytic lineage was enhanced by ␣-tocopherol treatment. ␣-Tocopherol treatment resulted in decreased basal phosphorylation of ERK1/2, PKC, and STAT-5 in HSC/HP cells. In contrast, ␣-tocopherol enhanced ERK1/2 activation in response to IL-3 stimulation in HSC/HP cells without altering the expression of IL-3Rs. Moreover, ␣-tocopherol-induced differentiation and ERK1/2 activation were abolished in mice pretreated with a MEK inhibitor (PD98059); however, pretreatment with PD98059 did not reduce the ␣-tocopherol-mediated increase in HSC/HP cells but instead, further enhanced their proliferation. Therefore, ␣-tocopherol induces expansion of HSC/HP cells by a nonidentified intracellular pathway and granulocytic/monocytic differentiation through ERK1/2 activation.
Biochimica et Biophysica Acta (BBA) - General Subjects, 2012
Background: Sleep is a physiological event that directly influences health by affecting the immun... more Background: Sleep is a physiological event that directly influences health by affecting the immune system, in which calcium (Ca 2+ ) plays a critical signaling role. We performed live cell measurements of cytosolic Ca 2+ mobilization to understand the changes in Ca 2+ signaling that occur in splenic immune cells after various periods of sleep deprivation (SD). Methods: Adult male mice were subjected to sleep deprivation by platform technique for different periods (from 12 to 72 h) and Ca 2+ intracellular fluctuations were evaluated in splenocytes by confocal microscopy. We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca 2+ mobilization in endoplasmic reticulum and mitochondria. Additionally, Ca 2+ channel gene expression was evaluated Results: Splenocytes showed a progressive loss of intracellular Ca 2+ maintenance from endoplasmic reticulum (ER) stores. Transient Ca 2+ buffering by the mitochondria was further compromised. These findings were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca 2+ channels. Conclusions and general significance: These novel data suggest that SD impairs Ca 2+ signaling, most likely as a result of ER stress, leading to an insufficient Ca 2+ supply for signaling events. Our results support the previously described immunosuppressive effects of sleep loss and provide additional information on the cellular and molecular mechanisms involved in sleep function.
Grape juice concentrate protects reproductive parameters of male rats against cadmium-induced damage: a chronic assay
British Journal of Nutrition, 2013
The aim of the present study was to investigate the effects of long-term grape juice concentrate ... more The aim of the present study was to investigate the effects of long-term grape juice concentrate (GJC) consumption, in two dosages, on the reproductive parameters of cadmium-exposed male rats. The effects of the concentrate on body mass gain, plasma testosterone levels, reproductive organ weights, daily sperm production, sperm morphology, testis histopathological and histomorphometrical parameters, and testicular antioxidant markers were investigated. Wistar rats (n 54) were distributed into six groups: CdCl2; cadmium and grape juice I (1·18 g/kg per d); cadmium and grape juice II (2·36 g/kg per d); grape juice I (1·18 g/kg per d); grape juice II (2·36 g/kg per d); control. A single dose of CdCl2 (1·2 mg/kg body weight (BW)) was injected intraperitoneally and the grape juice was administered orally for 56 d. The results indicated that cadmium changed all reproductive and antioxidant parameters. At dosage I (1·18 g/kg BW), GJC consumption did not show the effects against cadmium-induced damages. In contrast, at dosage II (2·36 g/kg BW), the GJC improved the gonadosomatic index (P= 0·003), serum testosterone levels (P= 0·001), the relative weight of epididymis (P= 0·013) and ventral prostate (P= 0·052), the percentage of normal sperm (P= 0·001), and histopathological and histomorphometrical parameters. In addition, at this dosage, normalisation of the enzymatic activity of superoxide dismutase (P= 0·001) and of testicular levels of glutathione (P= 0·03) were observed. The parameters of the non-exposed rats did not depict significant alterations. In conclusion, the product was able to act as a protector of reproductive function against cadmium-induced damage. Such a property was expressed in a dose-dependent manner as the more effective dose was dosage II. The GJC acted possibly by antioxidant mechanisms.
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Papers by Lisandro Lungato
secreted by activated macrophages. Considering that sleep is an
important physiological event that directly influences health and is
related to immune system function, our aim is to verify whether the
activity of CHIT is altered after paradoxical sleep deprivation (PSD)
and to assess the extent to which recovery sleep could affect this
biological process. Methods: We analyzed CHIT enzymatic activity
of Swiss and C57BL/6 mice and Wistar rats submitted to PSD for
72 hours without sleep rebound and with 24 hours of free sleep
following PSD. Results: We observed an increase in the activity of
plasma CHIT in PSD Swiss mice when compared to the Control
group (CT) (p < 0.05), C57BL/6 mice (p < 0.05) and Wistar rats
(p < 0.05). After 24 hours of sleep, no differences were observed
in rebound group (RG) compared to PSD Swiss mice (p > 0.05).
Moreover, differences were significant among RG C57BL/6 mice
(p < 0.05) and RG Wistar rats (p < 0.01) compared with their
respective PSD groups. Conclusions: Our data suggest that
CHIT is a relevant marker of macrophage activation, not only for
infections and diseases but also after 72h of PSD in mice and rats.
which calcium (Ca2+) plays a critical signaling role. We performed live cell measurements of cytosolic Ca2+
mobilization to understand the changes in Ca2+ signaling that occur in splenic immune cells after various
periods of sleep deprivation (SD).
Methods: Adult male mice were subjected to sleep deprivation by platform technique for different periods
(from 12 to 72 h) and Ca2+ intracellular fluctuations were evaluated in splenocytes by confocal microscopy.
We also performed spleen cell evaluation by flow cytometry and analyzed intracellular Ca2+ mobilization in
endoplasmic reticulum and mitochondria. Additionally, Ca2+ channel gene expression was evaluated
Results: Splenocytes showed a progressive loss of intracellular Ca2+ maintenance from endoplasmic reticulum
(ER) stores. Transient Ca2+ buffering by the mitochondria was further compromised. These findings
were confirmed by changes in mitochondrial integrity and in the performance of the store operated calcium
entry (SOCE) and stromal interaction molecule 1 (STIM1) Ca2+ channels.
Conclusions and general significance: These novel data suggest that SD impairs Ca2+ signaling, most likely as a
result of ER stress, leading to an insufficient Ca2+ supply for signaling events. Our results support the previously
described immunosuppressive effects of sleep loss and provide additional information on the cellular
and molecular mechanisms involved in sleep function.