CAROLINE CRISTIANO REAL GREGORIO
Projetos de Pesquisa
Unidades Organizacionais
LIM/43 - Laboratório de Medicina Nuclear, Hospital das Clínicas, Faculdade de Medicina
15 resultados
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- 11C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls: a cross-sectional study(2021) SOUZA, Aline Morais de; PITOMBEIRA, Milena Sales; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; REAL, Caroline Cristiano; FARIA, Daniele de Paula11C-PK11195 is a positron emitter tracer used for Positron Emission Tomography (PET) imaging of innate immune cell activation in studies of neuroinflammatory diseases. For the image quantitative analysis, it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition (plasma intact fraction). Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition. The purpose of this study is to compare 11C-PK11195 plasma metabolization rate between healthy controls and multiple sclerosis (MS) patients and evaluate the interference of sex, age, treatment, and disease phenotype in the tracer intact fraction measured in arterial plasma samples. 11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients (n = 50) and healthy controls (n = 23) at 20, 45, and 60 minutes after 11C-PK11195 injection. Analyses were also stratified by sex, age, treatment type, and MS phenotype. The results showed no significant differences in the metabolization rate of healthy controls and MS patients, or in the stratified samples. In conclusion, 11C-PK11195 metabolization has the same rate in patients with MS and healthy controls, which is not affected by sex, age, treatment, and disease phenotype. Thus, these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition, by using a population metabolization rate average. The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School (approval No. 624.065) on April 23, 2014.
- Neuroplasticity induced by the retention period of a complex motor skill learning in rats(2021) SAMPAIO, Adaneuda Silva Britto; REAL, Caroline Cristiano; GUTIERREZ, Rita Mara Soares; SINGULANI, Monique Patricio; ALOUCHE, Sandra Regina; BRITTO, Luiz Roberto; PIRES, Raquel SimoniLearning complex motor skills is an essential process in our daily lives. Moreover, it is an important aspect for the development of therapeutic strategies that refer to rehabilitation processes since motor skills previously acquired can be transferred to similar tasks (motor skill transfer) or recovered without further practice after longer delays (motor skill retention). Different acrobatic exercise training (AE) protocols induce plastic changes in areas involved in motor control and improvement in motor performance. However, the plastic mechanisms involved in the retention of a complex motor skill, essential for motor learning, are not well described. Thus, our objective was to analyze the brain plasticity mechanisms involved in motor skill retention in AE . Motor behavior tests, and the expression of synaptophysin (SYP), synapsin-I (SYS), and early growth response protein 1 (Egr-1) in brain areas involved in motor learning were evaluated. Young male Wistar rats were randomly divided into 3 groups: sedentary (SED), AE, and AE with retention period (AER). AE was performed three times a week for 8 weeks, with 5 rounds in the circuit. After a fifteen-day retention interval, the AER animals was again exposed to the acrobatic circuit. Our results revealed motor performance improvement in the AE and AER groups. In the elevated beam test, the AER group presented a lower time and greater distance, suggesting retention period is important for optimizing motor learning consolidation. Moreover, AE promoted significant plastic changes in the expression of proteins in important areas involved in control and motor learning, some of which were maintained in the AER group. In summary, these data contribute to the understanding of neural mechanisms involved in motor learning in an animal model, and can be useful to the construction of therapeutics strategies that optimize motor learning in a rehabilitative context.
- Physical exercise protects against mitochondria alterations in the 6-hidroxydopamine rat model of Parkinson's disease(2020) FERREIRA, Ana Flavia Fernandes; BINDA, Karina Henrique; SINGULANI, Monique Patricio; PEREIRA, Carolina Parga Martins; FERRARI, Gustavo Duarte; ALBERICI, Luciane Carla; REAL, Caroline Cristiano; BRITTO, Luiz RobertoParkinson's disease (PD) is typicaly caractherized by loss of dopaminergic neurons, as well as the presence of mitochondrial impairments. Although physical exercise is known to promote many beneficial effects in healthy subjects, such as enhancing mitocondrial biogenesis and function, it is not clear if these effects are evident after exercise in individuals with PD. The aim of this study was to investigate the effects of two different protocol durations on motor behavior (aphomorphine and gait tests), mitochondrial biogenesis signaling (PGC-1 alpha, NRF-1 and TFAM), structure (oxidative phosphorylation system protein levels) and respiratory chain activity (complex I) in a unilateral PD rat model. For this, male Wistar rats were injected with 6-hydroxydopamine unilaterally into the striatum and submitted to an intermitent moderate treadmill exercise for one or four weeks. In the gait test, only stride width data revealed an improvement after one week of exercise. On the other hand, after 4 weeks of the exercise protocol all gait parameters analyzed and the aphomorphine test demonstrated a recovery. Analysis of protein revealed that one week of exercise was able to prevent PGC-1 alpha and NRF-1 expression decrease in PD animals. In addition, after four weeks of physical exercise, besides PGC-1 alpha and NRF-1, reduction in TFAM and complex I protein levels and increased complex I activity were also prevented in PD animals. Thus, our results suggest a neuroprotective and progressive effect of intermittent treadmill exercise, which could be related to its benefits on mitochondrial biogenesis signaling and respiratory chain modulation of the dopaminergic system in PD.
- Cannabidiol Treatment Improves Glucose Metabolism and Memory in Streptozotocin-Induced Alzheimer's Disease Rat Model: A Proof-of-Concept Study(2022) FARIA, Daniele de Paula; SOUZA, Larissa Estessi de; DURAN, Fabio Luis de Souza; BUCHPIGUEL, Carlos Alberto; BRITTO, Luiz Roberto; CRIPPA, Jose Alexandre de Souza; FILHO, Geraldo Busatto; REAL, Caroline CristianoAn early and persistent sign of Alzheimer's disease (AD) is glucose hypometabolism, which can be evaluated by positron emission tomography (PET) with F-18-2-fluoro-2-deoxy-D-glucose ([F-18]FDG). Cannabidiol has demonstrated neuroprotective and anti-inflammatory properties but has not been evaluated by PET imaging in an AD model. Intracerebroventricular (icv) injection of streptozotocin (STZ) is a validated model for hypometabolism observed in AD. This proof-of-concept study evaluated the effect of cannabidiol treatment in the brain glucose metabolism of an icv-STZ AD model by PET imaging. Wistar male rats received 3 mg/kg of STZ and [F-18]FDG PET images were acquired before and 7 days after STZ injection. Animals were treated with intraperitoneal cannabidiol (20 mg/kg-STZ-cannabidiol) or saline (STZ-saline) for one week. Novel object recognition was performed to evaluate short-term and long-term memory. [F-18]FDG uptake in the whole brain was significantly lower in the STZ-saline group. Voxel-based analysis revealed a hypometabolism cluster close to the lateral ventricle, which was smaller in STZ-cannabidiol animals. The brain regions with more evident hypometabolism were the striatum, motor cortex, hippocampus, and thalamus, which was not observed in STZ-cannabidiol animals. In addition, STZ-cannabidiol animals revealed no changes in memory index. Thus, this study suggests that cannabidiol could be an early treatment for the neurodegenerative process observed in AD.
- Potential of [C-11](R)-PK11195 PET Imaging for Evaluating Tumor Inflammation: A Murine Mammary Tumor Model(2022) SOUZA, Aline Morais de; REAL, Caroline Cristiano; JUNQUEIRA, Mara de Souza; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; CHAMMAS, Roger; SAPIENZA, Marcelo Tatit; FARIA, Daniele de PaulaBackground: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [C-11](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. Methods: Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [C-11](R)-PK11195 and [F-18]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. Results: The [C-11](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [F-18]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [C-11](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. Conclusion: The [C-11](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [F-18]FDG, molecular imaging with [C-11](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.
- Development of a platform for the production of multiple modal chelating and imaging agents using desferrioxamine and bovine albumin as a model(2021) CORREIA, Lucas Antonio Arias; GARCIA, Rodrigo Santos; REAL, Caroline Cristiano; UZUELI, Daniel Henrique; SA, Ulisses Lacerda de Figueiredo; MARQUES, Fabio Luiz Navarro; COLNAGO, Luiz Alberto; ESPOSITO, Breno PanniaThe linker p-SCN-Bz-desferrioxamine was used as a conjugating agent to bovine serum albumin. The conjugate (BSA-DFO) did not display relevant structural alterations in comparison with the native protein. BSA-DFO was able to bind iron in a high affinity, antioxidant form similar to the native siderophore desferrioxamine. The gadolinium complex of BSA-DFO displayed 7-10 times higher relaxivities compared to the low molecular weight complex. Preparation of the radiotracers(68)Ga(BSA-DFO) and(89)Zr(BSA-DFO) in high radiochemical yields was accomplished quickly in mild conditions. These results indicate that BSA-DFO might be useful as an alternative treatment for iron overload disorders, and as a platform for the production of radiotracers or contrast agents for magnetic resonance imaging.
- [18F]FDG and [11C]PK11195 PET imaging in the evaluation of brown adipose tissue-effects of cold and pharmacological stimuli and their association with crotamine intake in a male mouse model(2023) FARIA, Daniele de Paula; CAMPEIRO, Joana D'Arc; JUNQUEIRA, Mara de Souza; REAL, Caroline Cristiano; MARQUES, Fabio Luiz Navarro; HAYASHI, Mirian Akemi Furuie; SAPIENZA, Marcelo TatitThis study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). Methods: Male C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6-9 degrees C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. Results: The cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 & PLUSMN; 1.05 vs. 2.03 & PLUSMN; 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 & PLUSMN; 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 & PLUSMN; 0.39; 21 days crotamine: 4.77 & PLUSMN; 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 & PLUSMN; 0.66 vs. 3.36 & PLUSMN; 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 & PLUSMN; 0.58, p = 0.7864) and also after CL stimulus (3.55 & PLUSMN; 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions: [11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C] PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.
- Endogenous protection against the 6-OHDA model of Parkinson's disease in the Amazonian rodent Proechimys(2019) MARQUES, Marcia Jonathas Guimaraes; REAL, Caroline Cristiano; VICTORINO, Daniella Balduino; BRITTO, Luiz Roberto; CAVALHEIRO, Esper Abrao; SCORZA, Fulvio Alexandre; FERRAZ, Henrique Ballalai; SCORZA, Carla AlessandraBackground Proechimys, an epilepsy-resistant rodent from Amazon Rainforest, is a promising alternative animal model for studying neurodegenerative disorders. Objectives: To evaluate behavioral and immunohistological changes in Proechimys after 6 - OHDA-induced model of PD. Methods: Following unilateral injections of 6 - OHDA into striatum, animals were assessed for exploratory behavior using the cylinder test. Brain sections were submitted to immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (lba-1). Results: We observed normal exploratory behavior during cylinder test in all animals. We could not detect changes in the expression of TH in both striatum and SNc, suggesting that Proechimys is resistant to dopaminergic neuronal degeneration. Glial activation was observed by an increase in Iba-1 expression in both striatum and SNc, and by an increase in GFAP expression in striatum. Conclusions: Proechimys represents a promising animal model for studying the mechanisms underlying the susceptibility of dopaminergic neurons to degeneration induced by 6 - OHDA.
- Motor improvement requires an increase in presynaptic protein expression and depends on exercise type and age(2018) GUTIERREZ, Rita Mara Soares; REAL, Caroline Cristiano; SCARANZI, Catharine Ranieri; GARCIA, Priscila Crespo; OLIVEIRA, Dalton Lustosa; BRITTO, Luiz Roberto; PIRES, Raquel SimoniThe aging process is associated with structural and functional changes in the nervous system. Considering that exercise can improve the quality of life of the elderly, the aim of this study was to evaluate the effects of exercise protocols with different motor demands on synaptic protein expression (i. e., synapsin-I and synaptophysin). Cognitive and motor brain areas and the motor performance of adult and aged animals were analyzed. Adult (7 months old) and aged (18 months old) male Wistar rats were used. Animals were divided into the following groups: treadmill exercise (TE, rhythmic motor activity), acrobatic exercise (AE, complex motor activity) and sedentary (SED, control). The animals were exposed to exercise 3 times per week for 8 weeks. The brains were collected for immunohistochemistry and immunoblotting assays. Our results showed that both types of exercise induced changes in motor performance and synaptic protein expression in adult and aged animals. However, acrobatic exercise promoted a greater number of changes, mainly in the aged animals. In addition, protein expression changes occurred in a greater number of brain areas in the aged animals than in adult animals. There were clear increases in synapsin-I expression in all areas analyzed of aged animals only after acrobatic exercises. On the other hand, synaptophysin increased in the same areas but with both types of exercise. Thus, in general, our data suggest that even at advanced ages, when the aging process is already in progress, initiating physical training may be beneficial to generate neuroplasticity that can improve motor performance.
- Sex-specific regulation of miR-22 and ERα in white adipose tissue of obese dam's female offspring impairs the early postnatal development of functional beige adipocytes in mice(2024) MENDONCA, Mariana de; BOLIN, Anaysa Paola; OLIVEIRA, Nayara Preste de; REAL, Caroline Cristiano; HU, Xiaoyun; HUANG, Zhan-Peng; WANG, Da-Zhi; RODRIGUES, Alice CristinaDuring inguinal adipose tissue (iWAT) ontogenesis, beige adipocytes spontaneously appear between postnatal 10 (P10) and P20 and their ablation impairs iWAT browning capacity in adulthood. Since maternal obesity has deleterious effects on offspring iWAT function, we aimed to investigate its effect in spontaneous iWAT browning in offspring. Female C57BL/6 J mice were fed a control or obesogenic diet six weeks before mating. Male and female offspring were euthanized at P10 and P20 or weaned at P21 and fed chow diet until P60. At P50, mice were treated with saline or CL316,243, a beta 3-adrenoceptor agonist, for ten days. Maternal obesity induced insulin resistance at P60, and CL316,243 treatment effectively restored insulin sensitivity in male but not female offspring. This discrepancy occurred due to female offspring severe browning impairment. During development, the spontaneous iWAT browning and sympathetic nerve branching at P20 were severely impaired in female obese dam's offspring but occurred normally in males. Additionally, maternal obesity increased miR-22 expression in the iWAT of male and female offspring during development. ER alpha, a target and regulator of miR22, was concomitantly upregulated in the male's iWAT. Next, we evaluated miR-22 knockout (KO) offspring at P10 and P20. The miR-22 deficiency does not affect spontaneous iWAT browning in females and, surprisingly, anticipates iWAT browning in males. In conclusion, maternal obesity impairs functional iWAT development in the offspring in a sex-specific way that seems to be driven by miR-22 levels and ER alpha signaling. This impacts adult browning capacity and glucose homeostasis, especially in female offspring.