Critical period of exposure to mercury and the diagnostic of autism spectrum disorder: A systematic review.

Autism spectrum disorder (ASD) is characterized by repetitive behaviors and deficits in social interaction. Its etiology is not completely clear, but both genetic and environmental factors contribute to and influence its development and course. The increased number of autism cases in recent years has been strongly associated with increased exposure to heavy metals. Mercury (Hg) has gained prominence in the scientific literature as a result of its presence as an urban pollutant and well-described neurotoxicity. This review assessed the relationship between Hg exposure in the pre- and post-natal period and ASD. The systematic review identified observational clinical studies and pre-clinical trials in journals indexed in the PubMed, Embase, ProQuest, and LILACS databases. The aim of this study was to investigate the association between exposure to Hg and ASD and to define the critical period of exposure. A total of 57 articles were selected for this review, with 35 articles (61.40%) identifying a positive association between ASD and Hg, while 22 articles (38.60%) did not find the same outcome. The biological samples most used to analyze Hg body burdens were hair (36.84%) and blood (36.84%). Most case-control studies found an increase in Hg levels in individuals with ASD who were exposed to a polluted environment in the post-natal period. Taken together, the studies suggest that these patients have a deficient detoxification system, and this could worsen the symptoms of the disorder. However, new studies addressing the influence of Hg on the post-natal nervous system and its relationship with ASD should be carried out.

L-carnitine and Acetyl-L Carnitine: A Possibility for Treating Alterations Induced by Obesity in the Central Nervous System.

Excessive consumption of nutrients, as well as obesity, leads to an inflammatory process, especially in adipose tissue. This inflammation reaches the systemic level and, subsequently, the central nervous system (CNS), which can lead to oxidative stress and mitochondrial dysfunction, resulting in brain damage. Thus, adequate treatment for obesity is necessary, including lifestyle changes (diet adequation and physical activity) and pharmacotherapy. However, these drugs can adversely affect the individual's health. In this sense, searching for new therapeutic alternatives for reestablishing metabolic homeostasis is necessary. L-carnitine (LC) and acetyl-L-carnitine (LAC) have neuroprotective effects against oxidative stress and mitochondrial dysfunction in several conditions, including obesity. Therefore, this study aimed to conduct a narrative review of the literature on the effect of LC and LAC on brain damage caused by obesity, in particular, on mitochondrial dysfunction and oxidative stress. Overall, these findings highlight that LC and LAC may be a promising treatment for recovering REDOX status and mitochondrial dysfunction in the CNS in obesity. Future work should focus on better elucidating the molecular mechanisms behind this treatment.

Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a persistent impairment of social skills, including aspects of perception, interpretation, and response, combined with restricted and repetitive behavior. ASD is a complex and multifactorial condition, and its etiology could be attributed to genetic and environmental factors. Despite numerous clinical and experimental studies, no etiological factor, biomarker, and specific model of transmission have been consistently associated with ASD. However, an imbalance in cholesterol levels has been observed in many patients, more specifically, a condition of hypocholesterolemia, which seems to be shared between ASD and ASD-related genetic syndromes such as fragile X syndrome (FXS), Rett syndrome (RS), and Smith- Lemli-Opitz (SLO). Furthermore, it is known that alterations in cholesterol levels lead to neuroinflammation, oxidative stress, impaired myelination and synaptogenesis. Thus, the aim of this review is to discuss the cholesterol metabolic pathways in the ASD context, as well as in genetic syndromes related to ASD, through clinical observations and animal models. In fact, SLO, FXS, and RS patients display early behavioral markers of ASD followed by cholesterol disturbances. Several studies have demonstrated the role of cholesterol in psychiatric conditions and how its levels modulate brain neurodevelopment. This review suggests an important relationship between ASD pathology and cholesterol metabolism impairment; thus, some strategies could be raised - at clinical and pre-clinical levels - to explore whether cholesterol metabolism disturbance has a generally adverse effect in exacerbating the symptoms of ASD patients.