RESUMO
Exposure to environmental pollutants, such as metals, pesticides, and air pollutants during early life, is a risk factor for neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD). Our systematic review aimed to select and summarize more recent case-control studies that examined the association between prenatal and early postnatal exposure to environmental pollutants and NDDs. We searched five databases (Web of Science, PubMed, Embase, Scopus, Ovid), screened 2261 records, and included 24 eligible case-control studies. Meta-analyses were conducted on subgroups of at least three studies that shared both the outcome and the exposure. A noteworthy discovery from this literature review is the existence of non-linear or non-monotonic dose-response relationships between the exposure to certain metals and the risk of ASD. The meta-analysis revealed a significant association between exposure to particular matter (PM)10 during the first year of life and the risk of ASD. Overall, studies included in our systematic review indicate that exposure to several pollutants within the first three years of life was significantly associated with the risk of NDDs.
Assuntos
Poluentes Ambientais , Transtornos do Neurodesenvolvimento , Humanos , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/toxicidade , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Estudos de Casos e Controles , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Exposição Ambiental/efeitos adversos , Gravidez , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/epidemiologia , Transtorno Autístico/etiologia , FemininoRESUMO
Micronutrients such as selenium (Se) are essentials since prenatal life to support brain and cognitive development. Se deficiency, which affects up to 1 billion people worldwide, can interact with common adverse environmental challenges including (Pb), exacerbating their toxic effects. Exploiting our recently validated rat model of maternal Se restriction and developmental low Pb exposure, our aims were to investigate: (i) the early consequences of suboptimal Se intake and low-Pb exposure on neuroinflammation in neonates' whole brains; (ii) the potential priming effect of suboptimal Se and low-Pb exposure on offspring's glial reactivity to a further inflammatory hit. To these aims female rats were fed with suboptimal (0.04 mg/kg; Subopt) and optimal (0.15 mg/kg; Opt) Se dietary levels throughout pregnancy and lactation and exposed or not to environmentally relevant Pb dose in drinking water (12.5 µg/mL) since 4 weeks pre-mating. We found an overall higher basal expression of inflammatory markers in neonatal brains, as well as in purified microglia and organotypic hippocampal slice cultures, from the Subopt Se offspring. Subopt/Pb cultures were highly activated than Subopt cultures and showed a higher susceptibility to the inflammatory challenge lipopolysaccharide than cultures from the Opt groups. We demonstrate that even a mild Se deficiency and low-Pb exposure during brain development can influence the neuroinflammatory tone of microglia, exacerbate the toxic effects of Pb and prime microglial reactivity to subsequent inflammatory stimuli. These neuroinflammatory changes may be responsible, at least in part, for adverse neurodevelopmental outcomes.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Selênio , Humanos , Gravidez , Ratos , Animais , Feminino , Selênio/farmacologia , Chumbo/toxicidade , Microglia , Encéfalo , Exposição Materna/efeitos adversosRESUMO
Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and interaction and repetitive/stereotyped behaviors. In recent years, the role of microbiota-gut-brain axis in ASD pathogenesis received growing attention, appearing as an attractive therapeutic target. We provide a comprehensive overview of changes in microbiota composition in ASD murine models so far identified, and summarize the therapeutic approaches targeting the microbiota on ASD-like neurobehavioral profile. Although alterations in microbiota composition have been observed in both genetic and environmental murine models of ASD, a clear microbiota profile shared by different ASD murine models has not been identified. We documented substantial discrepancies among studies (often within the same model), likely due to several confounding factors (from sex and age of animals to housing conditions). Despite these limitations, ASD animal models (under standardized conditions) remain a useful tool to evaluate (i) the beneficial effects of manipulations of gut microbiota on behavioral abnormalities; (ii) underlying neurobiological mechanisms related to gut-brain axis; and (iii) to identify optimal time windows for therapeutic interventions.
Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Microbiota , Animais , Camundongos , Transtorno do Espectro Autista/terapia , Modelos Animais de DoençasRESUMO
BTBR is an inbred mouse strain that displays several behavioral alterations resembling the core symptoms of Autism Spectrum Disorder, including deficit in sociability. In the present study, we investigated whether the pup-induced maternal behavior in virgin female mice, a naturally rewarding behavior, is impaired in this strain similarly to social interaction with adult conspecifics. We firstly assessed the maternal responsiveness towards newly born pups expressed by either virgin female mice of the BTBR strain or of the normo-social B6 strain. Next, we examined in both strains the expression of c-Fos as a marker of neuronal activity in selected brain areas involved in the regulation of maternal behavior in rodents including the olfactory bulb, the medial preoptic area and the paraventricular nucleus (PVN). We also examined the effects of pup presentation on oxytocinergic neurons of the PVN, the major brain site of synthesis of oxytocin, which has a pivotal role in facilitation of maternal response and social responsiveness in general. As a final step, we assessed the c-Fos expression pattern comparing the effect of exposure to pups with that induced by exposure to another social stimulus, focusing on other areas implicated in maternal responsiveness as well as in the affective component of social behavior such as pyriform cortex and central and basolateral amygdala. Our data showed that BTBR virgin females are less responsive to presentation of pups in comparison to B6, in parallel with lower activation of brain areas implicated in the maternal and social responsiveness.
Assuntos
Comportamento Animal/fisiologia , Comportamento Materno/fisiologia , Bulbo Olfatório/metabolismo , Ocitocina/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Área Pré-Óptica/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Comportamento Social , Animais , Animais Recém-Nascidos , FemininoRESUMO
Huntington's disease (HD) is an inherited neurodegenerative disorder, characterized by impairment in motor, cognitive and psychiatric domains. Currently, there is no specific therapy to act on the onset or progression of HD. The marked neuronal death observed in HD is a main argument in favour of stem cells (SCs) transplantation as a promising therapeutic perspective to replace the population of lost neurons and restore the functionality of the damaged circuitry. The availability of rodent models of HD encourages the investigation of the restorative potential of SCs transplantation longitudinally. However, the results of preclinical studies on SCs therapy in HD are so far largely inconsistent; this hampers the individuation of the more appropriate model and precludes the comparative analysis of transplant efficacy on behavioural end points. Thus, this review will describe the state of the art of in vivo research on SCs therapy in HD, analysing in a translational perspective the strengths and weaknesses of animal studies investigating the therapeutic potential of cell transplantation on HD progression.