PMID- 28733900 OWN - NLM STAT- MEDLINE DCOM- 20190211 LR - 20190215 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 55 IP - 6 DP - 2018 Jun TI - The Putative Role of Environmental Mercury in the Pathogenesis and Pathophysiology of Autism Spectrum Disorders and Subtypes. PG - 4834-4856 LID - 10.1007/s12035-017-0692-2 [doi] AB - Exposure to organic forms of mercury has the theoretical capacity to generate a range of immune abnormalities coupled with chronic nitro-oxidative stress seen in children with autism spectrum disorder (ASD). The paper discusses possible mechanisms explaining the neurotoxic effects of mercury and possible associations between mercury exposure and ASD subtypes. Environmental mercury is neurotoxic at doses well below the current reference levels considered to be safe, with evidence of neurotoxicity in children exposed to environmental sources including fish consumption and ethylmercury-containing vaccines. Possible neurotoxic mechanisms of mercury include direct effects on sulfhydryl groups, pericytes and cerebral endothelial cells, accumulation within astrocytes, microglial activation, induction of chronic oxidative stress, activation of immune-inflammatory pathways and impairment of mitochondrial functioning. (Epi-)genetic factors which may increase susceptibility to the toxic effects of mercury in ASD include the following: a greater propensity of males to the long-term neurotoxic effects of postnatal exposure and genetic polymorphisms in glutathione transferases and other glutathione-related genes and in selenoproteins. Furthermore, immune and inflammatory responses to immunisations with mercury-containing adjuvants are strongly influenced by polymorphisms in the human leukocyte antigen (HLA) region and by genes encoding effector proteins such as cytokines and pattern recognition receptors. Some epidemiological studies investigating a possible relationship between high environmental exposure to methylmercury and impaired neurodevelopment have reported a positive dose-dependent effect. Retrospective studies, on the other hand, reported no relationship between a range of ethylmercury-containing vaccines and chronic neuropathology or ASD. On the basis of these results, we would argue that more clinically relevant research is required to examine whether environmental mercury is associated with ASD or subtypes. Specific recommendations for future research are discussed. FAU - Morris, G AU - Morris G AUID- ORCID: 0000-0002-2914-1128 AD - Tir Na Nog, Bryn Road seaside 87, Llanelli, Wales, SA152LW, UK. activatedmicroglia@gmail.com. FAU - Puri, B K AU - Puri BK AD - Department of Medicine, Hammersmith Hospital, Imperial College London, London, W12 0HS, UK. FAU - Frye, R E AU - Frye RE AD - Division of Child and Adolescent Neurology and Children's Learning Institute, Department of Pediatrics, University of Texas, Austin, TX, USA. FAU - Maes, M AU - Maes M AD - Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand. LA - eng PT - Journal Article PT - Review DEP - 20170722 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - FXS1BY2PGL (Mercury) SB - IM MH - Autism Spectrum Disorder/*etiology MH - Environmental Exposure/*adverse effects MH - Humans MH - Mercury/*toxicity MH - Oxidative Stress/*drug effects OTO - NOTNLM OT - Autism spectrum disorders OT - Cytokines OT - Immune OT - Inflammation OT - Mercury OT - Oxidative stress EDAT- 2017/07/25 06:00 MHDA- 2019/02/12 06:00 CRDT- 2017/07/23 06:00 PHST- 2017/03/19 00:00 [received] PHST- 2017/07/13 00:00 [accepted] PHST- 2017/07/25 06:00 [pubmed] PHST- 2019/02/12 06:00 [medline] PHST- 2017/07/23 06:00 [entrez] AID - 10.1007/s12035-017-0692-2 [pii] AID - 10.1007/s12035-017-0692-2 [doi] PST - ppublish SO - Mol Neurobiol. 2018 Jun;55(6):4834-4856. doi: 10.1007/s12035-017-0692-2. Epub 2017 Jul 22.