Microglia and Autism Spectrum Disorder: Overview of Current Evidence and Novel Immunomodulatory Treatment Options

Abstract

Autism spectrum disorder is a rapidly increasing heterogeneous neurodevelopmental syndrome, remarked by persistent deficit in social communication, and restricted, repetitive patterns of behavior and interest. Lately, maternal immune activation and micgroglial dysfunction in the developing brain have been gaining mounting evidence and leading to studies of various novel agents as potential treatment options. A few immunomodulatory treatment options-luteolin, minocycline, suramin, vitamin D, gut microbiota-are discussed in the current article, regarding the current understanding of their mechanisms and evidence for potential clinical use. More studies are warranted to understand their exact mechanisms of action and to verify efficacy and safety in human subjects.

Keywords: Autism spectrum disorder; Immunomodulatory therapy.; Maternal immune activation; Microglia.

Fig. 1

Schematic diagram of microglia and immunomodulatory treatments. Maternal immune activation (MIA) during pregnancy may be bridged to an increased risk of autistic behaviors in the offspring by defective microglial activation. Microglial activation results in the production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. Luteolin, minocycline, and suramin have been shown to block microglial activation and attenuate the levels of inflammatory cytokines. Vitamin D and gut microbiota are believed to reduce pro-inflammatory cytokines released from microglia.