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Advanced Neurology Microglia in autism spectrum disorder

Figure 1. Maternal immune activation promotes the secretion of inflammatory cytokines through the abnormal activation of microglia. External
stimulation, such as rubella virus, bacteria, and toxoplasma invasion, in the early pregnancy leads to the activation of the maternal immune system and the
secretion of inflammatory cytokines through the placenta, which can activate microglia in the fetal central nervous system. Subsequently, the microglia’s
original branched morphology changes to amoeba-like. High levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α interact with neurons, causing
aberrant neuronal functioning and ultimately resulting in autism spectrum disorder symptoms.

importance of the active engulfment of synaptic structures (I) synapses is disrupted in ASD patients. Appropriate
by microglia during neuronal development to maintain pruning of synapses by microglia is vital to ensure the
normal neuronal functions . In their physiological function of excitatory and inhibitory neurons. Therefore,
[20]
state, microglia have a role in removing pathogens and the aberrant pruning effect of microglia on the E/I balance
maintaining CNS stability, directing the remodeling of may be one of the pathological reasons for ASD. It has been
brain cells after infection, removing debris in pathogenic confirmed in animal experiments that abnormal microglial
infection, as well as restoring affected intracellular and phagocytosis will break the balance of E-I synapses and
extracellular connections. In addition, 50% of neurons eventually lead to the development of neurodevelopmental
undergo programmed cell death during normal brain disorders and advanced brain dysfunction, such as
[24]
development, and microglia dispose of these neuronal Alzheimer’s disease and ASD . However, the role of
corpses through phagocytosis. However, under specific E/I signaling in ASD is still controversial. Some studies
circumstances, the impairment of microglial functions, have found that the function of excitatory synapses is
which include phagocytosis and pruning, may lead to inhibited in Shank2- and Shank3-deficient mice . In
[25]
abnormalities in neuronal function , thus resulting in contrast, other studies have shown that the synaptic E/I
[21]
[26]
certain autistic manifestations. balance in the hippocampus inclines toward excitability .
Recent studies have observed the preferential elimination
At the postsynaptic level, previous studies have
identified significant neurological changes in the brain of of excitatory synapses by microglia in pathological and
physiological brains of mature rats. The impairments of
ASD patients, such as neuronal overgrowth and microglia microglia in pruning excitatory synapses would result
activation in the frontal cortex . Animal experiments in a predominance of excitatory signaling compared to
[18]
have revealed that autistic mice have significantly higher inhibitory signaling in the ASD brain. The intervention of
dendritic spine densities , which could be the result of the abnormal pruning process will be a practical approach
[22]
pruning abnormalities and decreased microglial ability to for ASD treatment in the future .
[16]
phagocytose synapses. In addition, the impaired synaptic
connections between neurons following infection, which 3.2. Microglia contribute to the progression of ASD
are caused by microglia, may also contribute to ASD . by mediating inflammatory pathways and cytokines
[23]
At the presynaptic level, several studies have shown Microglia are key immune cells of the CNS, and the
that the balance between excitatory (E) and inhibitory neuroinflammation that is mediated by microglia is

Volume 1 Issue 3 (2022) 3 https://doi.org/10.36922/an.v1i3.167