Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Xiong, Yang; Chen, Jianhui; Li, Yingbo

doi:10.3389/fnins.2023.1125428

Cited by 30 publications

(22 citation statements)

References 111 publications

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“…In contrast, MIA animal models showed increased microglia motility [ 109 ], activation [ 110 ] and proliferation. Increased numbers of microglia or upregulation of microglial activation could potentially affect NPC proliferation [ 111 ], impair neurite outgrowth, and/or lead to over-pruning of synapses, which in turn could disrupt neuronal circuitry development [ 112 ].…”

Section: How Inflammation Shapes the Cellular Landscape Leading To Asdmentioning

confidence: 99%

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Vacharasin,

Ward,

McCord

et al. 2024

Oxford Open Neuroscience

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Autism spectrum disorders (ASD) affect 1 in 36 people and is more often diagnosed in males than in females. Core features of ASD are impaired social interactions, repetitive behaviors and deficits in verbal communication. ASD is a highly heterogeneous and heritable disorder, yet its underlying genetic causes account only for up to 80% of the cases. Hence, a subset of ASD cases could be influenced by environmental risk factors. Maternal immune activation (MIA) is a response to inflammation during pregnancy, which can lead to increased inflammatory signals to the fetus. Inflammatory signals can cross the placenta and blood brain barriers affecting fetal brain development. Epidemiological and animal studies suggest that MIA could contribute to ASD etiology. However, human mechanistic studies have been hindered by a lack of experimental systems that could replicate the impact of MIA during fetal development. Therefore, mechanisms altered by inflammation during human pre-natal brain development, and that could underlie ASD pathogenesis have been largely understudied. The advent of human cellular models with induced pluripotent stem cell (iPSC) and organoid technology is closing this gap in knowledge by providing both access to molecular manipulations and culturing capability of tissue that would be otherwise inaccessible. We present an overview of multiple levels of evidence from clinical, epidemiological, and cellular studies that provide a potential link between higher ASD risk and inflammation. More importantly, we discuss how stem cell-derived models may constitute an ideal experimental system to mechanistically interrogate the effect of inflammation during the early stages of brain development.

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Section: How Inflammation Shapes the Cellular Landscape Leading To Asdmentioning

confidence: 99%

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Vacharasin,

Ward,

McCord

et al. 2024

Oxford Open Neuroscience

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show abstract

“…GM plays a critical role in regulating the immune system as evidenced by the fact that dysbiosis, or alterations in the composition of GM, can lead to an inflammatory response in the gut, which can propagate to CNS through a variety of mechanisms, including the vagus nerve and circulating cytokines [89,90]. Indeed, it is now well-recognized that microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in ASD [91].…”

Section: Gut Microbiota -Microgliamentioning

confidence: 99%

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Tizabi¹,

Bennani²,

Kouhen³

et al. 2023

Preprint

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Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and social communication manifests in early childhood and is followed by significant impairment in social and occupational functions in adolescence and adulthood. Although genetics have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes including anemia, encephalopathy, gastroenteric diseases and more importantly cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as “Gut-Brain Axis (GBA).” In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. Potential exploitation of this interaction for therapeutic purposes is also touched upon.

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“…Despite differences in clinical profiles, genetics, and symptoms among neurological diseases, many central nervous system (CNS) disorders share substantial similarities in cerebrovascular impairments and immune dysregulation associated with neuroinflammation as the underlying pathophysiological mechanism of disease [1,2]. In particular, the role of the neuroimmune axis in the pathogenesis of neurodevelopmental disorders, including autism spectrum disorder (ASD), has been the focus of intense research during the past decade [3][4][5][6]. The hallmarks of ASD are social and behavioural deficits, often associated with intellectual disabilities, hyperactivity, anxiety, epilepsy and cognitive impairments [7,8].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the efficacy of a full-spectrum medicinal cannabis plant extract with less than 0.3% Δ9-tetrahydrocannabinol inin vitromodels of inflammation and excitotoxicity

Ross-Munro,

Isikgel,

Fleiss

2024

Preprint

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The rapid development of research on the therapeutic benefits of medicinal cannabis, in parallel with an increased understanding of the endocannabinoid system, has driven research of Cannabis sativa constituents for managing neurological conditions. While most studies have focused on the therapeutic potential of the major components of cannabis plant extract isolated or combined, limited research has explored the pharmacological benefits of whole cannabis plant extract. In this study, we investigated the potential anti-inflammatory and neuroprotective effects of NTI-164, a novel full-spectrum cannabis extract with negligible Delta9-tetrahydrocannabinol (THC), compared with cannabidiol (CBD) alone in BV-2 microglial and SHSY-5Y neuronal cells. The inflammation-induced upregulation of microglial inflammatory mediators, being tumour necrosis factor α (TNFalpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS), and Arginase-1 (Arg-1), were significantly attenuated by NTI-164. This immunomodulatory effect was not observed upon treatment with isolated CBD. Compared to CBD alone, NTI-164 prevented elevated mitochondrial activity while normalising cell numbers in immune-activated microglia cells. NTI-164 also promoted the proliferation of undifferentiated neurons and the survival of differentiated neurons under excitotoxic conditions. Overall, our work shows that the anti-inflammatory and neuroprotective effects of NTI-164 as a full-spectrum cannabis extract are enhanced relative to that of CBD alone, highlighting the potential therapeutic efficacy of NTI-164 for the treatment of neuropathologies such as autism spectrum disorder (ASD) and related neuropathologies. This study has further shown that understanding the synergistic effect of phytocannabinoids is integral to realising the therapeutic potential of full-spectrum cannabis extract to inform the design of botanical-derived treatments for managing neurological disorders.

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Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder

Cited by 30 publications

References 111 publications

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Neuroimmune mechanisms in autism etiology - untangling a complex problem using human cellular models

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

Evaluation of the efficacy of a full-spectrum medicinal cannabis plant extract with less than 0.3% Δ9-tetrahydrocannabinol inin vitromodels of inflammation and excitotoxicity

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