The role of neuropathological markers in the interpretation of neuropsychiatric disorders: Focus on fetal and perinatal programming

Fanni, Daniela; Gerosa, Clara; Rais, Monica; Ravarino, Alberto; Eyken, Peter Van; Fanos, Vassilios; Faa, Gavino

doi:10.1016/j.neulet.2016.10.063

Cited by 11 publications

(8 citation statements)

References 92 publications

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“…The vulnerability of the brain is key, essentially because there is no question that a number of chemicals, and certainly NPs, can interfere with the highly precise neurodevelopmental processes taking place in intrauterine life [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 24 , 25 , 26 , 27 , 45 , 46 , 47 , 48 , 91 , 96 ]. Of critical importance is the relationship between intrauterine toxic exposures and risk for major neurological, psychiatric, and cardiovascular diseases, a subject discussed for a number of years since the pioneering work of Barker [ 19 ] and 21 century researchers discussing fetal and perinatal programming and neuropsychiatric, metabolic, and cardiovascular diseases [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…NP (used here interchangeably with UFPM) size, shape, charge, surface composition, coating with biocompatible molecules, corona formation, and, certainly, stage of embryonic/fetus/placental maturation are key factors impacting free radical oxidative stress, inflammation, restricted placental growth, and the activation of placental toll-like receptors (TLRs), to name a few [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. There is a deep concern regarding uterine environmental exposures, the developmental origins of disease, and the fetal programming model predicting lifelong consequences from early intrauterine and/or postnatal exposures to insults significant in length, cumulative doses, and properties favoring specific cell damage [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Experimentally, NPs cause fetal developmental toxicity, and the early stages of brain organogenesis are highly vulnerable to reactive oxygen species (ROS); ultrastructural alterations in mitochondria, endoplasmic reticulum (ER), and Golgi complexes; downregulation of neuronal glutamate transporters; and, ultimately, the impairment of cognition and alterations in animal behavior [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Environmental Nanoparticles Reach Human Fetal Brains

et al. 2022

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Anthropogenic ultrafine particulate matter (UFPM) and industrial and natural nanoparticles (NPs) are ubiquitous. Normal term, preeclamptic, and postconceptional weeks(PCW) 8–15 human placentas and brains from polluted Mexican cities were analyzed by TEM and energy-dispersive X-ray spectroscopy. We documented NPs in maternal erythrocytes, early syncytiotrophoblast, Hofbauer cells, and fetal endothelium (ECs). Fetal ECs exhibited caveolar NP activity and widespread erythroblast contact. Brain ECs displayed micropodial extensions reaching luminal NP-loaded erythroblasts. Neurons and primitive glia displayed nuclear, organelle, and cytoplasmic NPs in both singles and conglomerates. Nanoscale Fe, Ti, and Al alloys, Hg, Cu, Ca, Sn, and Si were detected in placentas and fetal brains. Preeclamptic fetal blood NP vesicles are prospective neonate UFPM exposure biomarkers. NPs are reaching brain tissues at the early developmental PCW 8–15 stage, and NPs in maternal and fetal placental tissue compartments strongly suggests the placental barrier is not limiting the access of environmental NPs. Erythroblasts are the main early NP carriers to fetal tissues. The passage of UFPM/NPs from mothers to fetuses is documented and fingerprinting placental single particle composition could be useful for postnatal risk assessments. Fetal brain combustion and industrial NPs raise medical concerns about prenatal and postnatal health, including neurological and neurodegenerative lifelong consequences.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Environmental Nanoparticles Reach Human Fetal Brains

et al. 2022

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“…This means a great opportunity to search for new highly sensitive and specific biomarkers for early diagnosis of ASD, risk of regressive ASD [247], and further disorders in neurodevelopment and psychopathology, up to adulthood [248,249]. In a similar way to that of other neuropsychiatric disorders, ASD may be closely associated with several maternal, fetal, and perinatal epigenetic factors that influence brain development and maturation [250,251]. Metabolomics allows the discovery of biomarkers for an early diagnosis and the monitoring of fetal and perinatal programming [252].…”

Section: Metabolomics: a Promising 'Meaningful Web' Describing A Biochemical Fingerprintmentioning

confidence: 99%

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift

Panisi

Guerini

Abruzzo

et al. 2021

JPM

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The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called ‘First 1000 Days’) are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

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“…In other words, metabolomics describes the individual molecular phenotype, and allows monitoring of its changes over time through a “meaningful web” representing the individual “biochemical fingerprint”. Growing evidence highlights a wide array of applications of metabolomics in the study of neurodevelopmental and neuropsychiatric disorders, such as monitoring of fetal and perinatal programming for risk of neurodevelopmental/neuropsychiatric disorders [ 192 , 193 , 194 ], diagnosis of neurodevelopmental and psychiatric disorders [ 195 , 196 ], early diagnosis of ASD, risk of regressive ASD [ 197 ], correlation between metabolome and clinical phenotype in ASD [ 198 ]. The most discriminant metabolites in ASD are involved in amino acid metabolism, antioxidant status, mitochondrial function, and nicotinic acid metabolism [ 199 ].…”

Section: The Web Of Metabolic Immunologic and Microbiologic Imbalance...mentioning

confidence: 99%

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

Panisi¹,

Marini

2022

Brain Sciences

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The first step for a harmonious bio-psycho-social framework in approaching autism spectrum disorders (ASD) is overcoming the conflict between the biological and the psychosocial perspective. Biological research can provide clues for a correct approach to clinical practice, assuming that it would lead to the conceptualization of a pathogenetic paradigm able to account for epidemiologic and clinical findings. The upward trajectory in ASD prevalence and the systemic involvement of other organs besides the brain suggest that the epigenetic paradigm is the most plausible one. The embryo-fetal period is the crucial window of opportunity for keeping neurodevelopment on the right tracks, suggesting that women’s health in pregnancy should be a priority. Maladaptive molecular pathways beginning in utero, in particular, a vicious circle between the immune response, oxidative stress/mitochondrial dysfunction, and dysbiosis-impact neurodevelopment and brain functioning across the lifespan and are the basis for progressive multisystemic disorders that account for the substantial health loss and the increased mortality in ASD. Therefore, the biological complexity of ASD and its implications for health requires the enhancement of clinical skills on these topics, to achieve an effective multi-disciplinary healthcare model. Well-balanced training courses could be a promising starting point to make a change.

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The role of neuropathological markers in the interpretation of neuropsychiatric disorders: Focus on fetal and perinatal programming

Cited by 11 publications

References 92 publications

Environmental Nanoparticles Reach Human Fetal Brains

Environmental Nanoparticles Reach Human Fetal Brains

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

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