Impact of Sex and Age on the Mevalonate Pathway in the Brain: A Focus on Effects Induced by Maternal Exposure to Exogenous Compounds

Tonini, Claudia; Segatto, Marco; Pallottini, Valentina

doi:10.3390/metabo10080304

Cited by 6 publications

(6 citation statements)

References 116 publications

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“…These results contrast previous studies demonstrating that prenatal exposure to BPA trough drinking water showed enhanced hepatic transcription of Acc and Srebp1c genes in female rats [23], although this difference may be due to different doses or ages of the experimental models used; moreover, gene transcription does not always mean protein expression. It has been demonstrated that maternal exposure to low doses of BPA during gestation and lactation produces life-long dimorphic modulations in metabolic homeostasis in rat offspring [51,52].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

et al. 2021

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“…Increased levels of brain isoprenoids FPP and GGPP have been detected in hyperglycemia, where RhoC is induced in the liver by proinflammatory cytokines and in male Alzheimer patients [ 101 , 102 ]. These sex-dependent alterations in the mevalonate flux have been reported in both the liver and brain, where marked differences in regions involved in memory and learning functions could be at the basis of clinically relevant differences among males and females in both neurodevelopmental and neurodegenerative diseases [ 103 ]. Interestingly, FPP has been recently reported to act as a danger signal in the brain, inducing neuronal death in a mouse stroke model through the activation of transient receptor potential melastatin 2 [ 104 ].…”

Section: Neuroinflammation Oxidative Stress and Fever As A Consequenc...mentioning

confidence: 99%

Prenylation Defects and Oxidative Stress Trigger the Main Consequences of Neuroinflammation Linked to Mevalonate Pathway Deregulation

Pisanti

Rimondi

Pozza

et al. 2022

IJERPH

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The cholesterol biosynthesis represents a crucial metabolic pathway for cellular homeostasis. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids, and other molecules such as ubiquinone. Furthermore, some intermediates of this metabolic system perform biological activity in specific cellular compartments, such as isoprenoid molecules that can modulate different signal proteins through the prenylation process. The defects of prenylation represent one of the main causes that promote the activation of inflammation. In particular, this mechanism, in association with oxidative stress, induces a dysfunction of the mitochondrial activity. The purpose of this review is to describe the pleiotropic role of prenylation in neuroinflammation and to highlight the consequence of the defects of prenylation.

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“…The use of precursors of cholesterol is an option that might be explored. Mevalonic acid, the product of the first step of cholesterol synthesis, is present in blood and can be administered as a supplement [47,48]. We have been unable to find reliable data on the possibility that mevalonate crosses the BBB, therefore it is suggested that this possibility may be explored in experimental animals.…”

Section: Is It Possible To Supply Cholesterol To the Brain Of Asd Patients?mentioning

confidence: 99%

Cholesterol in autism spectrum disorders

Franco

Rivas‐Santisteban

Navarro

et al. 2021

Explor Neuroprot Ther

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The autism spectrum disorder (ASD) comprises a series of neurological diseases that share serious alterations of the development of the central nervous system. The degree of disability may vary so that Asperger’s may have a relatively normal life and get positions of responsibility in corporations and even in Governments, whereas other ASD sufferers are fully dependent on caregivers and have serious cognitive deficits. Although the first cases of autism were detected by looking at failures in metabolism, e.g., phenylketonuria, to later identify the faulty gene, today the trend is the opposite, first obtaining the exome and minimizing the look for altered parameters in blood, urine, etc. Cholesterol is key for neural development as it is not able to cross the blood brain barrier. Therefore, any gene or environmental factor that affects cholesterol synthesis will impact early developmental stages eventually leading to a disease within the autism spectrum and/or schizophrenia. This review provides data of the relevance of cholesterol dyshomeostasis in autism spectrum disorders. Determining biochemical parameters in body fluids should help to provide new therapeutic approaches in some cases of autism.

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Impact of Sex and Age on the Mevalonate Pathway in the Brain: A Focus on Effects Induced by Maternal Exposure to Exogenous Compounds

Cited by 6 publications

References 116 publications

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Prenatal Exposure to BPA: The Effects on Hepatic Lipid Metabolism in Male and Female Rat Fetuses

Prenylation Defects and Oxidative Stress Trigger the Main Consequences of Neuroinflammation Linked to Mevalonate Pathway Deregulation

Cholesterol in autism spectrum disorders

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