Role of Microglia in Autism: Recent Advances

Takano, Tomoyuki

doi:10.1159/000398791

Cited by 106 publications

(97 citation statements)

References 70 publications

(78 reference statements)

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“…Indeed, recent neuropathological studies in human post-mortem brains have revealed strong microglial activation in neurodevelopmental disorders, such as schizophrenia (de Baumont et al, 2015; Sekar et al, 2016), and ASD (Voineagu et al, 2011; Gupta et al, 2014; Takano, 2015). …”

Section: Microglial Perturbations During Brain Developmentmentioning

confidence: 99%

Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits

Paolicelli

Ferretti

2017

Front. Synaptic Neurosci.

159

126

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Many diverse factors, ranging from stress to infections, can perturb brain homeostasis and alter the physiological activity of microglia, the immune cells of the central nervous system. Microglia play critical roles in the process of synaptic maturation and brain wiring during development. Any perturbation affecting microglial physiological function during critical developmental periods could result in defective maturation of synaptic circuits. In this review, we critically appraise the recent literature on the alterations of microglial activity induced by environmental and genetic factors occurring at pre- and early post-natal stages. Furthermore, we discuss the long-lasting consequences of early-life microglial perturbation on synaptic function and on vulnerability to neurodevelopmental and psychiatric disorders.

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Section: Microglial Perturbations During Brain Developmentmentioning

confidence: 99%

Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits

Paolicelli

Ferretti

2017

Front. Synaptic Neurosci.

159

126

View full text Add to dashboard Cite

show abstract

“…Given that immune-system-related genes are not highly prevalent among the genetic candidates for ASD risk, alterations in the expression and methylation of immune genes in ASD may occur in reaction to abnormal neurodevelopment and/or in response to environmental factors. Microglia are observed to be activated in the ASD brain 88 ; however, differences in microglial-specific methylation patterns in ASD are currently unknown.…”

Section: Dna Methylation In Asdmentioning

confidence: 99%

The landscape of DNA methylation amid a perfect storm of autism aetiologies

2016

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Increasing evidence points to a complex interplay between genes and the environment in autism spectrum disorder (ASD), including rare de novo mutations in chromatin genes such as methyl-CpG binding protein 2 (MECP2) in Rett syndrome. Epigenetic mechanisms such as DNA methylation act at this interface, reflecting the plasticity in metabolic and neurodevelopmentally regulated gene pathways. Genome-wide studies of gene sequences, gene pathways and DNA methylation are providing valuable mechanistic insights into ASD. The dynamic developmental landscape of DNA methylation is vulnerable to numerous genetic and environmental insults: therefore, understanding pathways that are central to this ‘perfect storm’ will be crucial to improving the diagnosis and treatment of ASD.

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“…The presence of activated microglia has been reported in the dorsolateral prefrontal cortex of autistic patients [30]. Moreover, Positron Emission Tomography (PET) imaging studies have revealed an activation of microglia in other brain regions [31, 32]. Postmortem studies of individuals with ASD have also shown activation of microglia, as well as an increase in density [30, 33, 34].…”

Section: Evidence Of Neuroinflammatory Processes In Autismmentioning

confidence: 99%

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

et al. 2016

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Several genetic causes of autism spectrum disorder (ASD) have been identified. However, more recent work has highlighted that certain environmental exposures early in life may also account for some cases of autism. Environmental insults during pregnancy, such as infection or malnutrition, seem to dramatically impact brain development. Maternal viral or bacterial infections have been characterized as disruptors of brain shaping, even if their underlying mechanisms are not yet fully understood. Poor nutritional diversity, as well as nutrient deficiency, is strongly associated with neurodevelopmental disorders in children. For instance, imbalanced levels of essential fatty acids, and especially polyunsaturated fatty acids (PUFAs), are observed in patients with ASD and other neurodevelopmental disorders (e.g., attention deficit hyperactivity disorder (ADHD) and schizophrenia). Interestingly, PUFAs, and specifically n-3 PUFAs, are powerful immunomodulators that exert anti-inflammatory properties. These prenatal dietary and immunologic factors not only impact the fetal brain, but also affect the microbiota. Recent work suggests that the microbiota could be the missing link between environmental insults in prenatal life and future neurodevelopmental disorders. As both nutrition and inflammation can massively affect the microbiota, we discuss here how understanding the crosstalk between these three actors could provide a promising framework to better elucidate ASD etiology.

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Role of Microglia in Autism: Recent Advances

Cited by 106 publications

References 70 publications

Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits

Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits

The landscape of DNA methylation amid a perfect storm of autism aetiologies

Neuroinflammation in Autism: Plausible Role of Maternal Inflammation, Dietary Omega 3, and Microbiota

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