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Advanced Neurology Microglia in autism spectrum disorder

centrally involved in CNS injury and disease processing. increased risk of ASD. Besides, IL-6 cytokines form a
Microglia can be categorized into two phenotypes, the positive feedback loop by activating MAPK signaling, thus
pro-inflammatory M1 type and the anti-inflammatory exacerbating inflammation.
M2 type . M1 microglia, which induce neurotoxicity,
[27]
can secrete pro-inflammatory cytokines and chemokines 3.2.2. Inflammatory cytokines
such as interleukin (IL)-1β, IL-6, and tumor necrosis The increased release of inflammatory factors is closely
factor (TNF)-α. The neuroprotective M2 phenotype associated with the development of ASD. The expression
contributes to regulating inflammation with specific of inflammatory molecules, such as IL-1β, IL-6, IL-8,
cytokines, such as IL-10 and transforming growth factor IL-17, and TNF, has been found to be elevated in ASD,
(TGF)-β, as well as neurotrophic growth factors, such as and it has been suggested that the severity of the ASD
brain derived neurotrophic factor (BDNF) and glial cell- phenotype might be positively correlated with the pro-
derived neurotrophic factor (GDNF) . The balance of inflammatory cytokine concentration . Among them,
[28]
[36]
M1/M2 paradigm underlies different neuropathological pro-inflammatory cytokines IL-1β and IL-6, released by
conditions in ASD and is essential for CNS hemostasis. It is activated microglia, might have a role in neuronal damage
widely believed that an abnormal inflammatory response and significantly affect ASD . In addition, maternal
[37]
induced by M1 microglia may be an etiology of ASD. infection or inflammatory immune activation during
Microglia regulate neuroinflammation through specific pregnancy may drive microglia activation and promote
[18]
inflammatory pathways, such as nuclear factor kappa pro-inflammatory cytokine release, which would, in turn,
B (NF-κB), mitogen-activated protein kinase (MAPK), exacerbate the inflammatory response.
IL-1β, IL-6, IL-8, IL-17, and TNF. The dysregulation of
these pathways will affect neuronal activity and result in IL-1β is a key pro-inflammatory cytokine that is involved
ASD-like symptoms. in various autoimmune inflammatory responses and
cellular activities, such as cell multiplication, differentiation,
3.2.1. Inflammatory pathways and apoptosis. The synthesis and release of IL-1β are
[38]
The inflammatory pathway of NF-κB that is regulated by tightly regulated, and its expression is upregulated in
microglia plays an important role in mediating immune acute inflammatory, chronic inflammatory, and auto-
[39]
response . The initiation of the NF-κB signaling pathway inflammatory diseases . Microglia can produce large
[29]
[40]
and the transcription of cytokines involved in directing the amounts of IL-1β within the CNS . Abnormal IL-1β
immune response are required following an infection to levels may be responsible for neurological deficits of the
clear the invading pathogenic bacteria. Therefore, the NF-κB brain in ASD. In a study of serum extracellular vesicles in
[41]
signaling pathway is closely associated with inflammatory children with ASD, Tsilioni et al. found that the IL-1β
diseases and regulates the expression of genes encoding levels in these children were remarkably higher than the
[30]
[42]
immune response proteins . Inflammatory cytokines, controls following microglia activation. Another study
[31]
infection markers, or stress-activated protein kinases found elevated IL-1β levels in children with degenerative
[32]
can induce the activation of the NF-κB pathway . ASD and that IL-1β regulates the proliferation of neural
Within the CNS, the abnormal activation of the NF-κB precursor cells, suggesting that elevated IL-1β levels in the
[43]
signaling cascade leads to an abnormal expression of brain of ASD patients may alter neuronal development
[36]
pro-inflammatory cytokines, which may disrupt normal and affect postnatal neural development .
neuronal activity . A large number of literature works IL-8 is a pro-inflammatory cytokine, secreted by
[33]
have reported that the activation of microglial NF-κB various cells, including macrophages and microglia. IL-8
pathway may be involved in the regulation of ASD . functions primarily as a neutrophil chemotactic factor in
[34]
The MAPK signaling pathway also plays a key role the blood. This pro-inflammatory cytokine that is released
in inflammation and can be activated by cytokines, from microglia increases in response to pro-inflammatory
stress mediators, and inflammatory markers. Microglia stimuli. Elevated peripheral IL-8 levels have been observed
activation can also induce the MAPK signaling cascade, in psychiatric disorders, such as major depression, bipolar
which is primarily influenced by the activation of affective disorder, schizophrenia, sleep disorders, ASD,
toll-like receptors during inflammation, resulting in anxiety disorders, and dementia . In a clinical study
[44]
[35]
the phosphorylation of transcription factors . Once conducted by Bryn et al. , serum IL-8 concentrations
[45]
phosphorylated, the transcription factors translocate to the were significantly elevated in children with ASD compared
nucleus and transcribe genes encoding pro-inflammatory to healthy controls; this finding validates the role of
cytokines, such as IL-6 and TNF-α, thus promoting a peripheral IL-8 associated with microglia in ASD. Another
neuroinflammatory environment and leading to an study found that ASD patients have higher IL-8 levels in the
[17]
Volume 1 Issue 3 (2022) 4 https://doi.org/10.36922/an.v1i3.167