23 results on '"Tonini, Claudia"'
Search Results
2. Mechanisms of Sigma‐2/TMEM97 Involvement in Cholesterol Metabolism.
- Author
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Parente, Martina, Tonini, Claudia, Caputo, Sara, Fiocchetti, Marco, and Pallottini, Valentina
- Published
- 2024
- Full Text
- View/download PDF
3. Laparoscopic surgery for benign adnexal conditions under spinal anaesthesia: Towards a multidisciplinary minimally invasive approach
- Author
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Raimondo, Diego, Borghese, Giulia, Mastronardi, Manuela, Mabrouk, Mohamed, Salucci, Paolo, Lambertini, Agnese, Casadio, Paolo, Tonini, Claudia, Meriggiola, Maria Cristina, Arena, Alessandro, Tarozzi, Giulia, and Seracchioli, Renato
- Published
- 2020
- Full Text
- View/download PDF
4. Regulation of cholesterol metabolism: New players for an old physiological process.
- Author
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Parente, Martina, Tonini, Claudia, Segatto, Marco, and Pallottini, Valentina
- Published
- 2023
- Full Text
- View/download PDF
5. Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome.
- Author
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Parente, Martina, Tonini, Claudia, Buzzelli, Valeria, Carbone, Emilia, Trezza, Viviana, and Pallottini, Valentina
- Subjects
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FRAGILE X syndrome , *CHOLESTEROL metabolism , *CHOLESTEROL , *ANIMAL models in research , *BLOOD cholesterol , *AUTISM spectrum disorders , *HYDROXYCHOLESTEROLS - Abstract
Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-Δexon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-Δexon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
6. Long-lasting impact of perinatal dietary supplementation of omega 3 fatty acids on mevalonate pathway: potential role on neuron trophism in male offspring hippocampal formation.
- Author
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Tonini, Claudia, Schiavi, Sara, Macca, Fabrizio, Segatto, Marco, Trezza, Viviana, and Pallottini, Valentina
- Subjects
- *
NERVE growth factor , *FATTY acids , *OMEGA-3 fatty acids , *HIPPOCAMPUS (Brain) , *NEURONS - Abstract
Objective: We were aimed at evaluating the long-term impact of perinatal an omega-3 fatty acid-enriched diet on the mevalonate/cholesterol pathway in the brain of male offspring. Methods: Female rats were fed with standard or omega-3 fatty acid-enriched diet during pregnancy and lactation. Liver, brain and plasma were collected from infant, adolescent and adult male offspring for subsequent biochemical and morphological analyses. Results: The omega-3 enriched diet induced region-dependent changes of the 3-hydroxy 3-methylglutaryl Coenzyme A reductase in the brain and affected notably RhoA/CREB signaling and the nerve growth factor content in the hippocampus. Our data reveal a long-lasting impact of perinatal omega-3 fatty acid supplementation on hippocampal nerve growth factor levels mediated by reduced 3-hydroxy 3-methylglutaryl Coenzyme A reductase activation state and enhanced CREB signaling. Discussion: These data underline the importance of the perinatal omega-3 enriched diet for adult brain function and reveal a new pathway important for nerve growth factor regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. A Short‐Term Western Diet Impairs Cholesterol Homeostasis and Key Players of Beta Amyloid Metabolism in Brain of Middle Aged Rats.
- Author
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Spagnuolo, Maria Stefania, Pallottini, Valentina, Mazzoli, Arianna, Iannotta, Lucia, Tonini, Claudia, Morone, Barbara, Ståhlman, Marcus, Crescenzo, Raffaella, Strazzullo, Maria, Iossa, Susanna, and Cigliano, Luisa
- Published
- 2020
- Full Text
- View/download PDF
8. Prenatal exposure to valproate induces sex‐, age‐, and tissue‐dependent alterations of cholesterol metabolism: Potential implications on autism.
- Author
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Cartocci, Veronica, Tonini, Claudia, Di Pippo, Tiziana, Vuono, Florenzia, Schiavi, Sara, Marino, Maria, Trezza, Viviana, and Pallottini, Valentina
- Subjects
- *
AUTISM spectrum disorders , *PRENATAL exposure delayed effects , *CHOLESTEROL metabolism , *GENE regulatory networks , *HOMEOSTASIS - Abstract
Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex‐dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA. Our results show that physiological sex‐dependent differences are present both in the liver and in brain of rats. Interestingly, VPA affects specifically the brain in an age‐ and region‐specific manner; indeed, cerebellum, cortex, hippocampus and nucleus accumbens are affected in a sex‐dependent way, while this does not occur in amygdala and dorsal striatum. Overall, we demonstrate that each brain area responds differently to the same external stimulus and males and females respond in a different way, suggesting that this could be related to the diverse incidences, between the sexes, of some neurodevelopmental pathologies such as autism, which displays a 3:1 male to female ratio. Prenatal exposure to valproate (VPA) induces cholesterol metabolism alteration in brain. VPA‐induced cholesterol metabolism alterations are dimorphic and dependent on age. VPA‐induced cholesterol metabolism alterations could be related to autism spectrum disorder (ASD). [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses.
- Author
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Tonini, Claudia, Segatto, Marco, Bertoli, Simona, Leone, Alessandro, Mazzoli, Arianna, Cigliano, Luisa, Barberio, Laura, Mandalà, Maurizio, and Pallottini, Valentina
- Abstract
Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
10. Effects of Late-Life Caloric Restriction on Age-Related Alterations in the Rat Cortex and Hippocampus.
- Author
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Tonini, Claudia, Segatto, Marco, Martino, Francesca, Cigliano, Luisa, Nazzaro, Martina, Barberio, Laura, Mandalà, Maurizio, and Pallottini, Valentina
- Abstract
Background: A major problem of aging is the disruption of metabolic homeostasis. This is particularly relevant in the brain where it provokes neurodegeneration. Caloric restriction is a physiologic intervention known to delay the deleterious consequences of aging in several species ranging from yeast to mammals. To date, most studies on experimental models have started this dietary intervention from weaning, which is very difficult to be translated to human beings. Here, we study the effects of a more realistic dietary regimen in rats, starting at an advanced age and lasting for six months. Methods: we analyzed in the cortex and hippocampus, the proteins involved in the energetic balance of the cells, cholesterol metabolism, oxidative stress response, inflammation, synaptic impairment, and brain trophism. Results: our results suggest that caloric restriction in late life can revert only some age-related changes studied here. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
11. ProNGF/p75NTR Axis Drives Fiber Type Specification by Inducing the Fast-Glycolytic Phenotype in Mouse Skeletal Muscle Cells.
- Author
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Pallottini, Valentina, Colardo, Mayra, Tonini, Claudia, Martella, Noemi, Strimpakos, Georgios, Colella, Barbara, Tirassa, Paola, Bartolomeo, Sabrina Di, and Segatto, Marco
- Subjects
NERVE growth factor ,NEUROTROPHINS ,MUSCLE cells ,SKELETAL muscle physiology ,DUCHENNE muscular dystrophy ,MYOBLASTS ,SKELETAL muscle - Abstract
Despite its undisputable role in the homeostatic regulation of the nervous system, the nerve growth factor (NGF) also governs the relevant cellular processes in other tissues and organs. In this study, we aimed at assessing the expression and the putative involvement of NGF signaling in skeletal muscle physiology. To reach this objective, we employed satellite cell-derived myoblasts as an in vitro culture model. In vivo experiments were performed on Tibialis anterior from wild-type mice and an mdx mouse model of Duchenne muscular dystrophy. Targets of interest were mainly assessed by means of morphological, Western blot and qRT-PCR analysis. The results show that proNGF is involved in myogenic differentiation. Importantly, the proNGF/p75NTR pathway orchestrates a slow-to-fast fiber type transition by counteracting the expression of slow myosin heavy chain and that of oxidative markers. Concurrently, proNGF/p75NTR activation facilitates the induction of fast myosin heavy chain and of fast/glycolytic markers. Furthermore, we also provided evidence that the oxidative metabolism is impaired in mdx mice, and that these alterations are paralleled by a prominent buildup of proNGF and p75NTR. These findings underline that the proNGF/p75NTR pathway may play a crucial role in fiber type determination and suggest its prospective modulation as an innovative therapeutic approach to counteract muscle disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
12. Impact of Sex and Age on the Mevalonate Pathway in the Brain: A Focus on Effects Induced by Maternal Exposure to Exogenous Compounds.
- Author
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Tonini, Claudia, Segatto, Marco, and Pallottini, Valentina
- Subjects
MATERNAL exposure ,HYDROXYCHOLESTEROLS ,CHOLESTEROL ,AGE - Abstract
The mevalonate pathway produces cholesterol and other compounds crucial for numerous cellular processes. It is well known that age and sex modulate this pathway in the liver. Recently, similar effects were also noted in different brain areas, suggesting that alterations of the mevalonate pathway are at the root of marked sex-specific disparities in some neurodevelopmental disorders related to disturbed cholesterol homeostasis. Here, we show how the mevalonate pathway is modulated in a sex-, age- and region-specific manner, and how maternal exposure to exogenous compounds can disturb the regulation of this pathway in the brain, possibly inducing functional alterations. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
13. Maternal Dietary Exposure to Low-Dose Bisphenol A Affects Metabolic and Signaling Pathways in the Brain of Rat Fetuses.
- Author
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Tonini, Claudia, Segatto, Marco, Gagliardi, Simone, Bertoli, Simona, Leone, Alessandro, Barberio, Laura, Mandalà, Maurizio, and Pallottini, Valentina
- Abstract
Bisphenol A (BPA) is a synthetic compound widely used for the production of polycarbonate plasticware and epoxy resins. BPA exposure is widespread and more than 90% of individuals have detectable amounts of the molecule in their body fluids, which originates primarily from diet. Here, we investigated whether prenatal exposure to BPA affects the mevalonate (MVA) pathway in rat brain fetuses, and whether potential effects are sex-dependent. The MVA pathway is important for brain development and function. Our results demonstrate that the fetal brain, exposed in utero to a very low dose of BPA (2.5 µg/kg/day), displayed altered MVA pathway activation, increased protein prenylation, and a decreased level of pro-BDNF. Interestingly, the BPA-induced effects on estrogen receptor α were sex-dependent. In conclusion, this work demonstrates intergenerational effects of BPA on the brain at very low doses. Our results reveal new targets for BPA-induced interference and underline the impacts of BPA on health. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
14. Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins by JQ1 Unravels a Novel Epigenetic Modulation to Control Lipid Homeostasis.
- Author
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Tonini, Claudia, Colardo, Mayra, Colella, Barbara, Di Bartolomeo, Sabrina, Berardinelli, Francesco, Caretti, Giuseppina, Pallottini, Valentina, and Segatto, Marco
- Subjects
- *
LIPID metabolism , *CHOLESTEROL metabolism , *METABOLIC regulation , *LIPIDS , *HOMEOSTASIS , *PROTEINS , *BETAINE - Abstract
The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the management of lipid disorders. Here, we investigated the role of bromodomain and extraterminal domain (BET) proteins in the regulation of lipid metabolism. To reach this aim, we used a loss-of-function approach by treating HepG2 cells with JQ1, a powerful and selective BET inhibitor. The main results demonstrated that BET inhibition by JQ1 efficiently decreases intracellular lipid content, determining a significant modulation of proteins involved in lipid biosynthesis, uptake and intracellular trafficking. Importantly, the capability of BET inhibition to slow down cell proliferation is dependent on the modulation of cholesterol metabolism. Taken together, these data highlight a novel epigenetic mechanism involved in the regulation of lipid homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
15. Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome.
- Author
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Segatto, Marco, Tonini, Claudia, Pfrieger, Frank W., Trezza, Viviana, and Pallottini, Valentina
- Abstract
The mevalonate (MVA)/cholesterol pathway is crucial for central nervous system (CNS) development and function and consequently, any dysfunction of this fundamental metabolic pathway is likely to provoke pathologic changes in the brain. Mutations in genes directly involved in MVA/cholesterol metabolism cause a range of diseases, many of which present neurologic and psychiatric symptoms. This raises the question whether other diseases presenting similar symptoms are related albeit indirectly to the MVA/cholesterol pathway. Here, we summarized the current literature suggesting links between MVA/cholesterol dysregulation and specific diseases, namely autism spectrum disorder and Rett syndrome. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
16. Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome
- Author
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Martina Parente, Claudia Tonini, Valeria Buzzelli, Emilia Carbone, Viviana Trezza, Valentina Pallottini, Parente, Martina, Tonini, Claudia, Buzzelli, Valeria, Carbone, Emilia, Trezza, Viviana, and Pallottini, Valentina
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Autism Spectrum Disorder ,3-Hydroxy 3-methylglutaryl Coenzyme A reductase ,brain ,cholesterol ,Fmr1-Δexon 8 rat ,Fragile X Syndrome ,low-density lipoprotein receptor ,liver ,plasma ,prenylated proteins ,Catalysis ,Inorganic Chemistry ,Fragile X Mental Retardation Protein ,Animals ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,Organic Chemistry ,Brain ,General Medicine ,Computer Science Applications ,Biosynthetic Pathways ,Rats ,Cholesterol ,Fmr1-∆exon 8 rat - Abstract
Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-Δexon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-Δexon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target.
- Published
- 2022
17. Long-Lasting Impact of Sugar Intake on Neurotrophins and Neurotransmitters from Adolescence to Young Adulthood in Rat Frontal Cortex
- Author
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Maria Stefania Spagnuolo, Arianna Mazzoli, Martina Nazzaro, Antonio Dario Troise, Cristina Gatto, Claudia Tonini, Mayra Colardo, Marco Segatto, Andrea Scaloni, Valentina Pallottini, Susanna Iossa, Luisa Cigliano, Spagnuolo, Maria Stefania, Mazzoli, Arianna, Nazzaro, Martina, Troise, Antonio Dario, Gatto, Cristina, Tonini, Claudia, Colardo, Mayra, Segatto, Marco, Scaloni, Andrea, Pallottini, Valentina, Iossa, Susanna, Cigliano, Luisa, Spagnuolo, MARIA STEFANIA, and Troise, ANTONIO DARIO
- Subjects
Inflammation ,Adolescent rat · Frontal cortex · Fructose diet · Brain-derived neurotrophic factor · Neurotransmitters · Mitochondria · Inflammation ,Cellular and Molecular Neuroscience ,Neurology ,Fructose diet ,Neuroscience (miscellaneous) ,Adolescent rat ,Neurotransmitters ,Brain-derived neurotrophic factor ,Frontal cortex ,Mitochondria - Abstract
The detrimental impact of fructose, a widely used sweetener in industrial foods, was previously evidenced on various brain regions. Although adolescents are among the highest consumers of sweet foods, whether brain alterations induced by the sugar intake during this age persist until young adulthood or are rescued returning to a healthy diet remains largely unexplored. To shed light on this issue, just weaned rats were fed with a fructose-rich or control diet for 3 weeks. At the end of the treatment, fructose-fed rats underwent a control diet for a further 3 weeks until young adulthood phase and compared with animals that received from the beginning the healthy control diet. We focused on the consequences induced by the sugar on the main neurotrophins and neurotransmitters in the frontal cortex, as its maturation continues until late adolescence, thus being the last brain region to achieve a full maturity. We observed that fructose intake induces inflammation and oxidative stress, alteration of mitochondrial function, and changes of brain-derived neurotrophic factor (BDNF) and neurotrophin receptors, synaptic proteins, acetylcholine, dopamine, and glutamate levels, as well as increased formation of the glycation end-products Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL). Importantly, many of these alterations (BDNF, CML, CEL, acetylcholinesterase activity, dysregulation of neurotransmitters levels) persisted after switching to the control diet, thus pointing out to the adolescence as a critical phase, in which extreme attention should be devoted to limit an excessive consumption of sweet foods that can affect brain physiology also in the long term.
- Published
- 2022
18. Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses
- Author
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Alessandro Leone, Marco Segatto, Simona Bertoli, Arianna Mazzoli, Luisa Cigliano, Valentina Pallottini, Claudia Tonini, Maurizio Mandalà, Laura Barberio, Tonini, C., Segatto, M., Bertoli, S., Leone, A., Mazzoli, A., Cigliano, L., Barberio, L., Mandala, M., Pallottini, V., Tonini, Claudia, Segatto, Marco, Bertoli, Simona, Leone, Alessandro, Mazzoli, Arianna, Cigliano, Luisa, Barberio, Laura, Mandalà, Maurizio, and Pallottini, Valentina
- Subjects
0301 basic medicine ,Male ,Chemical compound ,bisphenol A ,010501 environmental sciences ,01 natural sciences ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Bisphenol A ,Pregnancy ,TX341-641 ,Fetu ,3-hydroxy 3-methylglutaryl coenzyme A reductase, acyl coenzyme A carboxylase, bisphenol A, cholesterol, fatty acids, fetuses, liver ,Benzhydryl Compound ,Nutrition and Dietetics ,Fetuse ,Lipid ,Lipids ,Cholesterol ,Liver ,In utero ,Prenatal Exposure Delayed Effects ,Female ,hormones, hormone substitutes, and hormone antagonists ,medicine.medical_specialty ,endocrine system ,Offspring ,Acyl coenzyme A carboxylase ,liver ,fatty acids ,Prenatal Exposure Delayed Effect ,Article ,3-hydroxy 3-methylglutaryl coenzyme A reductase ,Fatty acids ,Fetuses ,Animals ,Benzhydryl Compounds ,Estrogen Receptor alpha ,Fetus ,Inflammation ,Lipid Metabolism ,Phenols ,03 medical and health sciences ,Internal medicine ,medicine ,Prenatal exposure ,0105 earth and related environmental sciences ,Phenol ,Nutrition. Foods and food supply ,business.industry ,Animal ,urogenital system ,cholesterol ,Metabolism ,Fatty acid ,Rats ,030104 developmental biology ,Endocrinology ,chemistry ,Hepatic lipid ,fetuses ,acyl coenzyme A carboxylase ,Sprague-Dawley ,business ,Food Science - Abstract
Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.
- Published
- 2021
19. A Short-Term Western Diet Impairs Cholesterol Homeostasis and Key Players of Beta Amyloid Metabolism in Brain of Middle Aged Rats
- Author
-
Arianna Mazzoli, Luisa Cigliano, Susanna Iossa, Lucia Iannotta, Barbara Morone, Maria Stefania Spagnuolo, Maria Strazzullo, Valentina Pallottini, Claudia Tonini, Raffaella Crescenzo, Marcus Ståhlman, Stefania Spagnuolo, Maria, Pallottini, Valentina, Mazzoli, Arianna, Iannotta, Lucia, Tonini, Claudia, Morone, Barbara, Ståhlman, Marcu, Crescenzo, Raffaella, Strazzullo, Maria, Iossa, Susanna, Cigliano, Luisa, Spagnuolo, M. S., Pallottini, V., Mazzoli, A., Iannotta, L., Tonini, C., Morone, B., Stahlman, M., Crescenzo, R., Strazzullo, M., Iossa, S., and Cigliano, L.
- Subjects
0301 basic medicine ,Apolipoprotein E ,medicine.medical_specialty ,high fat–high fructose diet ,Apolipoprotein E, cholesterol, high fat-high fructose diet, hippocampus, middle age ,Nicastrin ,Fructose ,Biology ,Reductase ,Presenilin ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Apolipoproteins E ,Internal medicine ,medicine ,Amyloid precursor protein ,Insulin-degrading enzyme ,Cholesterol 24-Hydroxylase ,Animals ,Homeostasis ,middle age ,apolipoprotein E ,cholesterol ,high fat-high fructose diet ,hippocampus ,Liver X Receptors ,030109 nutrition & dietetics ,Amyloid beta-Peptides ,Membrane Glycoproteins ,hippocampu ,Cholesterol ,Age Factors ,Brain ,030104 developmental biology ,Endocrinology ,chemistry ,Receptors, LDL ,Blood-Brain Barrier ,Diet, Western ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl CoA Reductases ,Amyloid Precursor Protein Secretases ,Low Density Lipoprotein Receptor-Related Protein-1 ,Food Science ,Biotechnology ,Sterol Regulatory Element Binding Protein 2 - Abstract
Scope Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, the aim is to evaluate whether a diet rich in fat and fructose affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers of beta amyloid metabolism. Methods and results Middle aged rats are fed a high fat-high fructose (HFF) or a control diet for 4 weeks. Inflammatory markers and cholesterol levels significantly increase in hippocampus of HFF rats. A higher activation of 3-hydroxy 3-methylglutaryl coenzyme-A reductase, coupled with lower levels of apolipoprotein E, LXR-beta, and lipoproteins receptors is measured in hippocampus from HFF rats. The alteration of critical players of cholesterol homeostasis is associated with increased level of amyloid precursor protein, presenilin 1, and nicastrin, and decreased level of insulin degrading enzyme. Conclusions Overall these data show that a western diet is associated with perturbation of cholesterol homeostasis in middle aged rats, mostly in hippocampus. This might trigger molecular events involved in the onset of neurodegenerative diseases.
- Published
- 2020
20. Maternal Dietary Exposure to Low-Dose Bisphenol A Affects Metabolic and Signaling Pathways in the Brain of Rat Fetuses
- Author
-
Alessandro Leone, Simone Gagliardi, Laura Barberio, Simona Bertoli, Marco Segatto, Valentina Pallottini, Claudia Tonini, Maurizio Mandalà, Tonini, Claudia, Segatto, Marco, Gagliardi, Simone, Bertoli, Simona, Leone, Alessandro, Barberio, Laura, Mandalà, Maurizio, and Pallottini, Valentina
- Subjects
0301 basic medicine ,medicine.medical_specialty ,endocrine system ,bisphenol A ,Estrogen receptor ,Mevalonic Acid ,lcsh:TX341-641 ,3-Hydroxy 3-methylglutaryl Coenzyme A reductase ,neurotrophins ,Article ,Dietary Exposure ,cholesterol ,mevalonate pathway ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fetus ,Phenols ,Pregnancy ,Internal medicine ,medicine ,Animals ,Benzhydryl Compounds ,Nutrition and Dietetics ,biology ,Cholesterol ,urogenital system ,Brain ,Maternal Nutritional Physiological Phenomena ,Diet ,Rats ,030104 developmental biology ,Endocrinology ,chemistry ,In utero ,Maternal Exposure ,biology.protein ,Protein prenylation ,Female ,Mevalonate pathway ,Signal transduction ,lcsh:Nutrition. Foods and food supply ,030217 neurology & neurosurgery ,hormones, hormone substitutes, and hormone antagonists ,Food Science ,Neurotrophin ,Signal Transduction - Abstract
Bisphenol A (BPA) is a synthetic compound widely used for the production of polycarbonate plasticware and epoxy resins. BPA exposure is widespread and more than 90% of individuals have detectable amounts of the molecule in their body fluids, which originates primarily from diet. Here, we investigated whether prenatal exposure to BPA affects the mevalonate (MVA) pathway in rat brain fetuses, and whether potential effects are sex-dependent. The MVA pathway is important for brain development and function. Our results demonstrate that the fetal brain, exposed in utero to a very low dose of BPA (2.5 µ, g/kg/day), displayed altered MVA pathway activation, increased protein prenylation, and a decreased level of pro-BDNF. Interestingly, the BPA-induced effects on estrogen receptor &alpha, were sex-dependent. In conclusion, this work demonstrates intergenerational effects of BPA on the brain at very low doses. Our results reveal new targets for BPA-induced interference and underline the impacts of BPA on health.
- Published
- 2020
21. Prenatal exposure to valproate induces sex-, age- and tissue-dependent alterations of cholesterol metabolism: potential implications on autism
- Author
-
Veronica Cartocci, Tiziana Di Pippo, Sara Schiavi, Viviana Trezza, Maria Marino, Florenzia Vuono, Claudia Tonini, Valentina Pallottini, Cartocci, Veronica, Tonini, Claudia, Tiziana Di Pippo, Florenzia, Vuono, Schiavi, Sara, Marino, Maria, Trezza, Viviana, and Pallottini, Valentina
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Cerebellum ,Physiology ,Clinical Biochemistry ,Striatum ,Nucleus accumbens ,Stimulus (physiology) ,Amygdala ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sex Factors ,Western blot ,Pregnancy ,Risk Factors ,Internal medicine ,medicine ,Cholesterol, hydroxy-methylglutaryl Coenzyme A reductase, rats, sex, valproate ,Animals ,Protein Interaction Maps ,Autistic Disorder ,Rats, Wistar ,Sex Characteristics ,medicine.diagnostic_test ,Cholesterol ,business.industry ,Sexual Development ,Valproic Acid ,Age Factors ,Brain ,Cell Biology ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Liver ,Maternal Exposure ,030220 oncology & carcinogenesis ,Prenatal Exposure Delayed Effects ,Autism ,Anticonvulsants ,Female ,lipids (amino acids, peptides, and proteins) ,business - Abstract
Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex-dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA. Our results show that physiological sex-dependent differences are present both in the liver and in brain of rats. Interestingly, VPA affects specifically the brain in an age- and region-specific manner; indeed, cerebellum, cortex, hippocampus and nucleus accumbens are affected in a sex-dependent way, while this does not occur in amygdala and dorsal striatum. Overall, we demonstrate that each brain area responds differently to the same external stimulus and males and females respond in a different way, suggesting that this could be related to the diverse incidences, between the sexes, of some neurodevelopmental pathologies such as autism, which displays a 3:1 male to female ratio.
- Published
- 2019
22. Sex-, age- and region-dependent alterations of brain cholesterol metabolism: potential implications for autism spectrum disorder
- Author
-
Claudia Tonini, Veronica Cartocci, Sara Schiavi, Viviana Trezza, Valentina  , Pallottini, Mediterranenan Neuroscience Society, Tonini, Claudia, Cartocci, Veronica, Schiavi, Sara, Trezza, Viviana, Valentina,  , and Pallottini, Valentina
- Published
- 2019
23. Prenatal exposure to Bisphenol A induces alterations of cholesterol homeostasis in rat foetuses
- Author
-
Claudia Tonini, Simona Bertoli, Alessandra Colciago, Maurizio Mandalà Luana Ricci, Tullia Todros, Valentina Pallottini., Italian Physiological Society, Tonini, Claudia, Bertoli, Simona, Colciago, Alessandra, Mandalà Luana Ricci, Maurizio, Todros, Tullia, and Pallottini, Valentina
- Published
- 2018
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