Microglia: Synaptic modulator in autism spectrum disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable impairment of social communication and repetitive behaviors, highly restricted interests, and/or sensory behaviors beginning early in life. Many individuals with ASD have dysfunction of microglia, which may be closely related to neuroinflammation, making microglia play an important role in the pathogenesis of ASD. Mounting evidence indicates that microglia, the resident immune cells of the brain, are required for proper brain function, especially in the maintenance of neuronal circuitry and control of behavior. Dysfunction of microglia will ultimately affect the neural function in a variety of ways, including the formation of synapses and alteration of excitatory–inhibitory balance. In this review, we provide an overview of how microglia actively interact with neurons in physiological conditions and modulate the fate and functions of synapses. We put a spotlight on the multi-dimensional neurodevelopmental roles of microglia, especially in the essential influence of synapses, and discuss how microglia are currently thought to influence ASD progression.

Microglia-Derived Insulin-like Growth Factor 1 Is Critical for Neurodevelopment

“…Similarly, our study revealed the increased mean duration of grooming behavior, suggesting either a self-soothing mechanism or repetitive behavior [22,33]. Furthermore, microglial dysregulation is a prominent factor in the development of ASD [34]. These findings collectively suggest that microglial dysfunction leading to the suppression of Igf1 expression may contribute to the development of psychiatric disorders such as ASD.…”

Role of Natural Compounds Modulating Heme Catabolic Pathway in Gut, Liver, Cardiovascular, and Brain Diseases

“…This results in the downregulation of BLVRA in brain tumors, specifically, meningiomas and gliomas, with implications not yet elucidated with antioxidant status and chemoresistance in these tumor types [6,115]. Moreover, NFkB activation during hypoxic-ischemic injury [116] may contribute to the underlying cause of cerebral palsy [117][118][119][120] and autism spectrum disorders [121][122][123][124][125].…”

Unraveling the Endocannabinoid System: Exploring Its Therapeutic Potential in Autism Spectrum Disorder

“…During inflammation, 2-AG, which is a ligand of endocannabinoid receptor, is released from various immune cells and induces neuroprotection through several mechanisms by binding to endocannabinoid receptor (Zou & Kumar, 2018 ). Microglial cells and astrocytes produce 2-AG in response to intracellular Ca +2 and glutamate receptor stimulation, which stimulates purinergic P2X7 receptor (Carrier et al, 2004 ; Hu et al, 2022 ). The ECS, specially CB2 receptor, mediates T and B lymphocytes proliferation, apoptosis, macrophage-mediated killing of sensitized cells, production of inflammatory cytokines by the inhibiting cyclic AMP/ Protein kinase A (PKA) pathways, migration of B cells, and cytokines induction.…”

“…The ECS, specially CB2 receptor, mediates T and B lymphocytes proliferation, apoptosis, macrophage-mediated killing of sensitized cells, production of inflammatory cytokines by the inhibiting cyclic AMP/ Protein kinase A (PKA) pathways, migration of B cells, and cytokines induction. Dendritic cells also have the capability to undergo cannabinoid-induced apoptosis due to their immunosuppressive properties (Do et al, 2004 ; Hu et al, 2022 ). So, ECS can be a crucial target for ASD therapies due to its anti-inflammatory and immunosuppressive effects.…”

“…Targeting the ES receptor can lead to side effects like inhibition of learning and memory, hence the ES CB2 receptor, which is present in microglia, is being targeted nowadays. High levels of mRNA and protein of the CB2 receptor have been observed in the blood of autistic children, suggesting its essential role in ASD (Hu et al, 2022 ; Siniscalco et al, 2013 ). Various pharmacological molecules can be used to reduce microglia-mediated neurodegeneration and inflammation and beta-amyloid induced neurotoxicity by modulating various ECS receptors like CB1, CB2 and unknown receptors.…”