Synthesis and pharmacological evaluation of novel N-aryl-cinnamoyl-hydrazone hybrids designed as neuroprotective agents for the treatment of Parkinson's disease.

Molecular hybridization between structural fragments from the structures of curcumin (1) and resveratrol (2) was used as a designing tool to generate a new N-acyl-cinnamoyl-hydrazone hybrid molecular architecture. Twenty-eight new compounds were synthesized and evaluated for multifunctional activities related to Parkinson's disease (PD), including neuroprotection, antioxidant, metal chelating ability, and Keap1/Nrf2 pathway activation. Compounds 3b (PQM-161) and 3e (PQM-164) were highlighted for their significant antioxidant profile, acting directly as induced free radical stabilizers by DPPH and indirectly by modulating intracellular inhibition of t-BOOH-induced ROS formation in neuronal cells. The mechanism of action was determined as a result of Keap1/Nrf2 pathway activation by both compounds and confirmed by different experiments. Furthermore, compound 3e (PQM-164) exhibited a significant effect on the accumulation of α-synuclein and anti-inflammatory activity, leading to an expressive decrease in gene expression of iNOS, IL-1ß, and TNF-α. Overall, these results highlighted compound 3e as a promising and innovative multifunctional drug prototype candidate for PD treatment.

Internal dose rate due to intake of uranium and thorium by fish from a dam reservoir associated with a uranium mine in Brazil.

Uranium mining can cause environmental impacts on non-human biota around mine sites. Because of this, the reduction in non-human biota exposure becomes an important issue. Environmental radioprotection results from the evolution of human radioprotection; it is based on dose rate to non-human biota and uses, as a biological target, and has harmful effects on populations. In the present study, a flooded impoundment created following dam construction in a uranium mine plant undergoing decommissioning was investigated. Internal dose rates due to activity concentration of natural uranium (Unat) and 232Th in omnivorous, phytophagous, and carnivorous fish species were estimated. Radionuclide activity concentrations were obtained by spectrophotometry with arsenazo III in the visible range. The dose rate contribution of 232Th was lower than that of Unat. There were no differences between the internal dose rates to studied fish species due to 232Th, but there were differences for Unat. A dose rate of 2.30·10-2 µGy∙d-1 was found due to the two studied radionuclides. Although this value falls below the benchmark for harmful effects, it is important to acknowledge that the assessment did not account for other critical radionuclides from uranium mining, which also contribute to the internal dose. Moreover, the study did not assess external doses. As a result, the possibility cannot be excluded that dose rates at the study area overcome the established benchmarks for harmful effects.

Antinociceptive Effect of Dillenia indica (Linn.) Mediated by Opioid and Cannabinoid Systems: Pharmacological and Chemical Studies.

Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D. indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D. indica were submitted to an in vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D. indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as caffeoylmalic acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D. indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.

Alginate-Chitosan Membranes for the Encapsulation of Lavender Essential Oil and Development of Biomedical Applications Related to Wound Healing.

Biopolymers such as chitosan (CHT) or alginate (ALG) are among the most prominent for health-related applications due to their broad bioactivity. Their combination for the preparation of membranes is hereby proposed as an application for wound healing with the incorporation of lavender essential oil (LEO), widely known for its antioxidant and antimicrobial properties. The preparation of CHT, CHT + LEO, ALG, ALG + LEO, and CHT/ALG + LEO membranes was accomplished, and its composition was analyzed using Fourier Transform Infrared Spectroscopy (FTIR). The water absorption capacity and oil release profile of the membranes revealed higher water uptake capacity when a lower LEO release was obtained. The combined CHT/ALG + LEO film showed a water uptake percentage of 638% after 48 h and a maximum LEO release concentration of 42 mg/L. Cytotoxicity and biocompatibility of the prepared membranes were studied using a HaCaT cell line, with an assessment of cell viability regarding film leachables, DNA quantification, and DAPI-phalloidin staining. The results revealed that the indirect contact of the prepared membranes via its leachables does not compromise cell viability, and upon direct contact, cells do not adhere or proliferate on the surface of the membranes. Moreover, the CHT/ALG + LEO membrane increases cell proliferation, making it suitable for applications in wound healing.

Optical coherence tomography findings in fungal uveitis.

PURPOSE: The purpose of the study was to describe the vitreal, retinal, and choroidal features of eyes affected by endogenous endophthalmitis (EE) and evaluate the effects of systemic antifungal drug treatment and pars plana vitrectomy by using spectral domain optical coherence tomography (SD-OCT). METHODS: Medical records and SD-OCT images of eyes diagnosed with EE at a single uveitis tertiary referral center in Brazil were acquired at the time of diagnosis, after 7 days of high-dose antifungal drug treatment, and at follow-up assessments performed 30 days after resolution. RESULTS: Thirteen eyes were enrolled in the study. All patients showed hyperreflective round-shaped lesions on SD-OCT and pre-retinal aggregates. Five eyes responded to antifungal systemic oral drugs despite showing vitreous opacity. The response to treatment was observable on optical coherence tomography (OCT) images. CONCLUSION: Fungal endophthalmitis showed typical features on SD-OCT, facilitating early diagnosis and treatment despite the absence of vitreous culture or biopsy. This study suggests that OCT images can be used to support diagnosis by physicians who do not have access to vitreoretinal surgery.

On the not so anomalous water-induced structural transformations of choline chloride-urea (reline) deep eutectic system.

The choline chloride-urea binary mixture in the molar ratio (1 : 2), commonly known as reline, is an archetypal solvent among deep eutectic solvents (DES). Neutron diffraction (ND) and empirical potential structure refinement (EPSR) results provided evidence that reline exhibits a peculiar structural transformation upon water addition that manifests in a sudden dewetting of the choline cations at ∼51 wt% water and, therefore, a non-monotonic variation of the choline-water and choline-choline coordination. Here, we study, through molecular dynamics (MD), the influence of water on the structure of a choline chloride : urea : water DES (1 : 2 : ζ; ζ = 0 to 40), to gain additional insight into the molecular source of this peculiar structural transformation. Five different force fields were investigated. Our results show that the ND/EPSR non-monotonic behavior of the choline-choline coordination is qualitatively reproduced by those force fields that describe more accurately the dynamics of the DES, namely, the diffusion and viscosity coefficients. However, the apparent increase of the choline-choline coordination at ζ > 10 (41 wt%) is associated with the drain of a particular first coordination sphere, rather than with a dewetting of the choline cations, as predicted by ND/EPSR. Thus, a monotonic increase of the choline-water coordination is found instead, as well as the emergence of a tetrahedral hydrogen bond network of water, opposite to ND/EPSR. The highest rate of depletion upon initial hydration is found for urea around choline (∼0.9 urea molecules/ζ), whereas choline depicts the highest rate of hydration (∼2.5 water molecules/ζ). These rates decrease with ζ and a structural transition that stabilizes above 41 wt% is observed, consistent with ND/EPSR results. Despite limitations in the force fields, we argue that the experimental and simulation opposite pictures could be related to an underestimation of water's hydrogen bond network portrayed by the EPSR method. Overall, a smoother transition from a DES to an aqueous solution of the DES components is portrayed by MD, compared with ND/EPSR.

White wine grape pomace as a suitable carbon source for lipid and carotenoid production by fructophilic Rhodorotula babjevae.

AIM: We aim to explore the non-structural sugars from white wine grape pomace (WWGP) as the input carbon source for the co-production of multiple high-value products by the non-fastidious yeast Rhodotorula babjevae to create a sustainable and economically appealing process. METHODS AND RESULTS: Water extraction of unfermented, soluble sugars from WWGP yielded extracts with similar amounts of glucose and fructose, which were used to prepare a growth medium. Rhodorotula babjevae multiplied as fast on WWGP-based medium as on a reference medium but achieved higher cell dry weight (CDW) and lower intracellular triacylglycerol accumulation (22.5% vs. 28.6%) in WWGP-based medium. In addition, R. babjevae produced mannitol and arabitol and carotenoids and secreted polyol esters of fatty acids, a rare type of glycolipid as confirmed by Fourier transform-infrared, nuclear magnetic resonance and high-performance liquid chromatography analyses. Remarkably, R. babjevae consumed simultaneously both fructose and glucose when on WWGP-based medium and left glucose practically untouched in the reference medium, evidencing a fructophilic character. CONCLUSIONS: Rhodorotula babjevae, a metabolic versatile yeast, proliferated on a minimally processed extract and successfully converted glucose and fructose into high-value products. SIGNIFICANCE AND IMPACT OF STUDY: Different chemicals with market potential can be produced through the valorization of abundant waste feedstocks generated by the wine industry to which R. babjevae can contribute.

Prevalence of sarcopenia according to EWGSOP1 and EWGSOP2 in older adults and their associations with unfavorable health outcomes: a systematic review.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) recently updated the definition and diagnostic criteria to assess sarcopenia, which can result in important changes in sarcopenia prevalence in older adults. AIM: To compare the prevalence of sarcopenia through the diagnostic criteria and definition proposed by the first (EWGSOP1) and recent (EWGSOP2) European consensus in older adults. We also aimed to evaluate which sarcopenia consensus is better associated with unfavorable health outcomes. METHODS: The review followed PRISMA guidelines. Embase, Medline (PubMed), Scopus and Web of Science were searched from 2018 to February 2021. The systematic review protocol was registered at PROSPERO (CRD42020213303). The search, selection, and evaluation processes were done in a duplicate and independent manner. RESULTS: Of the 298 potentially eligible articles, 9 were included in this review. The prevalence of sarcopenia was 17.7% by EWGSOP1 and 11% by EWGSOP2. Evaluating all the studies, the sarcopenia prevalence ranged from 6.2 to 35.3% for the EWGSOP1, and from 3.2 to 26.3% for the EWGSOP2. Five studies have evaluated the association between the prevalence of sarcopenia (EWGSOP1 versus EWGSOP2) and unfavorable health outcomes, in which three studies showed that EWGSOP1 was better associated with increased risk of hospitalization and/or mortality. CONCLUSION: In comparison with EWGSOP1, the prevalence of sarcopenia in older adults decreased when diagnosed according to EWGSOP2. Based on limited evidence, EWGSOP2 seems to be worse for predicting unfavorable outcomes compared with EWGSOP1.

Unravelling the nature of citric acid:L-arginine:water mixtures: the bifunctional role of water.

The use of water as a component of deep eutectic systems (DES) has raised some questions regarding its influence on the nature of the mixture. Does it form a DES or an aqueous solution and what is the role of water? In this work, the nature of citric acid:l-arginine:water mixtures was explored through phase equilibria studies and spectroscopic analysis. In a first step, PC-SAFT was validated as a predictive tool to model the water influence on the solid liquid equilibria (SLE) of the DES reline using the individual-component approach. Hence, activity coefficients in the ternary systems citric acid:l-arginine:water and respective binary combinations were studied and compared using ePC-SAFT. It was observed that the water-free mixtures citric acid:l-arginine showed positive deviation from Raoult's law, while upon addition of water strong negative deviation from Raoult's law was found, yielding melting depressions around 100 K. Besides these strong interactions, pH was found to become acidic (pH = 3.5) upon water addition, which yields the formation of charged species ([H2Cit]- and [l-arg]+). Thus, the increased interactions between the molecules upon water addition might be caused by several mechanisms such as hydrogen bonding or ionic forces, both being induced by water. For further investigation, the liquid mixtures citric acid:l-arginine:water were studied by FTIR and NMR spectroscopy. FTIR spectra disproved a possible solubility enhancement caused by salt formation between citric acid and l-arginine, while NMR spectra supported the formation of a hydrogen bonding network different from the binary systems citric acid:water and l-arginine:water. Either being a DES or other type of non-ideal solution, the liquefaction of the studied systems is certainly caused by a water-mediator effect based on the formation of charged species and cross interactions between the mixture constituents.

Natural deep eutectic systems, an emerging class of cryoprotectant agents.

This work aimed at evaluating the potential of using natural deep eutectic systems (NADES) as cryoprotectant agents (CPAs). Several combinations between natural primary metabolites that have been identified in animals that live in extreme cold climates were prepared. All systems showed very little cytoxicity towards L929 cells at concentrations high as 1-2 M. Moreover, this cell line was highly tolerant to 10% (w/v) of NADES when compared to Me2SO. To test NADES as CPAs, two cell lines were used, L929 and HacaT cells. After freeze/thawing cycle, it was possible to observe that for L929 cells, NADES presented similar behaviour to Me2SO. For Hacat cell line a significant improvement on post-thawing recovery was observed. Moreover, the results presented herein showed that NADES do not need to be removed from the freezing media after thawing the cells, which is a great advantage of these materials. Additionally, we have shown that NADES can act as CPA when cells are frozen at -20 °C. In overall, the results demonstrate the high potential of NADES to be used in cryobiology as alternative CPAs.

The Role of Hydrogen Bond Donor on the Extraction of Phenolic Compounds from Natural Matrices Using Deep Eutectic Systems.

Recently, deep eutectic systems (DESs) as extraction techniques for bioactive compounds have surfaced as a greener alternative to common organic solvents. In order to study the effect of these systems on the extraction of phenolic compounds from different natural sources, a comprehensive review of the state of the art was carried out. In a first approach, the addition of water to these systems and its effect on DES physicochemical properties such as polarity, viscosity, and acidity was investigated. This review studied the effect of the hydrogen bond donor (HBD) on the nature of the extracted phenolics. The effects of the nature of the HBD, namely carbon chain length as well as the number of hydroxyl, methyl, and carbonyl groups, have shown to play a critical role in the extraction of different phenolic compounds. This review highlights the differences between DES systems and systematizes the results published in the literature, so that a more comprehensive evaluation of the systems can be carried out before any experimental trial.

Supercritical CO2 Assisted Impregnation of Ibuprofen on Medium-Chain-Length Polyhydroxyalkanoates (mcl-PHA).

In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl-PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g·h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer's crystallinity was also affected concomitantly with the matrices' ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.

Valorization of Cork Using Subcritical Water.

Granulated cork was submitted to subcritical water extraction/hydrolysis in a semi-continuous reactor at temperatures in the range of 120-200 °C and with a constant pressure of 100 bar. The influence of temperature on the composition of the cork extracts obtained was assessed-namely, their content of carbohydrates and phenolics. The extraction yield increased with the temperature, and this was associated with the decrease in the dielectric constant of water and the increase in its ionic product. Extracts composed of up to 36% phenolics were obtained at temperatures of up to 120 °C, with an antioxidant activity only two times lower than that of pure gallic acid, but in low amounts. Assays at higher temperatures generated extracts richer in carbohydrates and with a phenolics content of ca. 20 wt.% in comparatively far higher amounts. Neither the amount of suberin nor its structure were affected by the subcritical water treatment.

Maternal protein malnutrition induces autism-like symptoms in rat offspring.

Objective: We tested the correlation between maternal protein malnutrition and autistic-like symptoms using behavioral tests in rodents that measure main behavioral characteristics observed in humans with autism spectrum disorder (ASD). Methods: Pregnant female rats were fed a normal diet or a hypoproteic diet during gestation and lactation periods. The litters were weighed every 3 days during lactation, and the offspring were tested in behavioral tasks during infancy (postnatal day (PND) 5: quantification of ultrasonic vocalizations; PND 13: homing behavior test) and adolescence (PND 30-32: open field, hole-board, play social behavior, and object recognition tests) in order to capture the prevalence of some of the core and associated symptoms of ASD. Results: Litters of the hypoproteic diet group had a lesser weight gain during lactation. In addition, pups of dams fed with a hypoproteic diet vocalized less compared to those fed with a normal diet, and they showed impaired social discrimination abilities in the homing behavior test. In adolescence, both male and female offspring of the hypoproteic diet group showed no impairment in locomotor activity; however, they exhibited stereotypic behavior in the hole-board test and a decrease in social play behaviors. Male offspring showed increased interest in exploring a familiar object rather than a novel object. Conclusion: Our results show that maternal protein malnutrition in rats causes offspring behaviors that resemble core and associated ASD symptoms.

Could adverse effects and complications of selective laser trabeculoplasty be decreased by low-power laser therapy?

Selective laser trabeculoplasty (SLT) has been used for treatment of primary open-angle glaucoma, ocular hypertension, pigmenter and pseudoexfoliative glaucoma being considered a low-risk procedure. Therefore, transitory and permanent adverse effects have been reported, including corneal changes, subclinical edema, and reduction in endothelial cells and in central corneal thickness. Despite rarer, serious corneal complications after SLT can be permanent and lead to visual impairment, central corneal haze, opacity and narrowing. The mechanism involves increase of vasoactive and chemotactic cytokines causing inflammatory infiltrate, destruction of stromal collagen by fibroblasts and increase of matrix metalloproteinases type 2, which impair reepithelization. SLT also increases free radical production and reduces antioxidant enzymes, resulting in endothelium damages. Low-power laser therapy (LPLT) has been used in regenerative medicine based on its biostimulatory and anti-inflammatory effects. Biostimulation occurs through the interaction of laser photons with cytochrome C oxidase enzyme, which activates intracellular biochemical cascades causing synthesis of a number of molecules related to anti-inflammatory, regenerative effects, pain relief and reduction in edema. It has been showed that LPLT reduces gene expression related to pro-inflammatory cytokines and matrix metalloproteinases, and it increases expression of growth factors related to its proliferative and healing actions. Although radiations emitted by low-power lasers are considered safe and able to induce therapeutic effects, researches based on experimental models for glaucoma could bring important data if LPLT could be an alternative approach to improve acceptation for patients undergoing SLT.

Natural deep eutectic systems as alternative nontoxic cryoprotective agents.

Natural deep eutectic systems (NADES) are mostly composed of natural primary metabolites such as sugars, sugar alcohols, organic acids, amino acids and amines. These simple molecules have been identified in animals living in environments with extreme temperature amplitudes, being responsible for their survival at negative temperatures during winter. Herein, we report for the first time the use of NADES based on trehalose (Treh) and glycerol (Gly) in cryopreservation, as cryoprotective agents (CPA). The evaluation of the thermal behaviour of these eutectic systems, showed that NADES have a strong effect on the water crystallization/freezing and melting process, being able to reduce the number of ice crystals and hence ice crystal damage in cells, which is a crucial parameter for their survival, upon freezing. Using this NADES as CPA, it is possible to achieve similar or even better cellular performance when compared with the gold standard for cryopreservation dimethyl sulfoxide (DMSO). In this sense, this work relates the physical properties of the NADES with their biological performance in cryopreservation. Our comprehensive strategy results in the demonstration of NADES as a promising nontoxic green alternative to the conventional CPA's used in cryopreservation methods.

Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts.

The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective glass transition temperature, Tg = -54.3 °C, is in good agreement with the one predicted by the composition dependence of the Tg values determined for menthol:flurbiprofen therapeutic deep eutectic solvents (THEDESs). Nonisothermal crystallization was never observed for neat menthol loaded into silica hosts, which can indicate that menthol rests as a full amorphous/supercooled material inside the pores of the silica matrixes. Menthol mobility was probed by dielectric relaxation spectroscopy, which allowed to identify two relaxation processes in both pore sizes: a faster one associated with mobility of neat-like menthol molecules (α-process), and a slower, dominant one due to the hindered mobility of menthol molecules adsorbed at the inner pore walls (S-process). The fraction of molecular population governing the α-process is greater in the higher (5.9 nm) pore size matrix, although in both cases the S-process is more intense than the α-process. A dielectric glass transition temperature was estimated for each α (Tg,dielc(α)) and S (Tg,dielc(S)) molecular population from the temperature dependence of the relaxation times to 100 s. While Tg,dielc(α) agrees better with the value obtained from the linearization of the Fox equation assuming ideal behavior of the menthol:flurbiprofen THEDES, Tg,dielc(S) is close to the value determined by calorimetry for the silica composites due to a dominance of the adsorbed population inside the pores. Nevertheless, the greater fraction of more mobile bulk-like molecules in the 5.9 nm pore size matrix seems to determine the faster drug release at initial times relative to the 3.2 nm composite. However, the latter inhibits crystallization inside pores since its dimensions are inferior to menthol critical size for nucleation. This points to a suitability of these composites as drug delivery systems in which the drug release profile can be controlled by tuning the host pore size.

Protein malnutrition during pregnancy alters maternal behavior and anxiety-like behavior in offspring.

OBJECTIVE: The aim of this study was to evaluate the effects of protein malnutrition during pregnancy on maternal behavior, on the early behavior in pups by ultrasonic vocalizations (USVs) emission, and on the behavior of offspring in adulthood in an elevated T-maze. METHODS: Pregnant female rats were fed a normal protein-powdered diet (22% casein; control) or a low-protein (hypoproteic) diet (6% casein; protein restriction) during the first 2 weeks of pregnancy. On the fifth postpartum day (PND5), the number of USV was rated. On PND7, maternal behavior was assessed. Male offspring in adulthood were evaluated for behavioral performance in an elevated T-maze. RESULTS: Our results demonstrated that a hypoproteic diet during early pregnancy increased the maternal behavior, increased the number of USV by pups, and reduced the inhibitory avoidance responses in an elevated T-maze during adulthood. In addition, there was a reduction in weight gain of rats during pregnancy and of offspring during lactation. CONCLUSION: In conclusion, the data found in our study suggest that the increase in USV emitted by pups due to hypoproteic diet during pregnancy accentuated maternal behavior. In addition, an increase in maternal care promoted the reduction in anxiety-like behavior in adult male offspring.

Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin.

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.

Sickness behavior is delayed in hypothyroid mice.

Sickness behavior is an expression of a motivational state triggered by activation of the peripheral innate immune system, whereby an organism reprioritizes its functions to fight infection. The relationship between thyroid hormone and immune cells is complex, and additional insights are needed about the involvement of the cross-talk between thyroid hormone, the central nervous system and immune function, as demonstrated by the consequences to sickness behavior. The aim of this work was to evaluate sickness behavior in hypothyroid mice. Control mice and mice treated with propylthiouracil (PTU) for 30days (0.05%; added to drinking water) received a single dose of LPS (200µg/kg; i.p.) or saline, and the behavioral response was assessed for 24h. We provide evidence that thyroid status acts a modulator for the development of depressive-like and exploratory behaviors in mice that are subjected to an immunological challenge because the PTU pretreatment delayed the LPS-induced behavioral changes observed in an open field test and in a forced swimming test. This response was observed concomitantly with a lower thermal index until 4h after the LPS administration. This result demonstrates that thyroid status modifies behavioral responses to immune challenge and suggests that thyroid hormones are essential for the manifestation of sickness behavior during endotoxemia.