Mast cell‑mediated neuroinflammation may have a role in attention deficit hyperactivity disorder (Review)

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental and behavioral disorder with a serious negative impact on the quality of life from childhood until adulthood, which may cause academic failure, family disharmony and even social unrest. The pathogenesis of ADHD has remained to be fully elucidated, leading to difficulties in the treatment of this disease. Genetic and environmental factors contribute to the risk of ADHD development. Certain studies indicated that ADHD has high comorbidity with allergic and autoimmune diseases, with various patients with ADHD having a high inflammatory status. Increasing evidence indicated that mast cells (MCs) are involved in the pathogenesis of brain inflammation and neuropsychiatric disorders. MCs may cause or aggravate neuroinflammation via the selective release of inflammatory factors, interaction with glial cells and neurons, activation of the hypothalamic-pituitary adrenal axis or disruption of the blood-brain barrier integrity. In the present review, the notion that MC activation may be involved in the occurrence and development of ADHD through a number of ways is discussed based on previously published studies. The association between MCs and ADHD appears to lack sufficient evidence at present and this hypothesis is considered to be worthy of further study, providing a novel perspective for the treatment of ADHD.

An Shen Ding Zhi Ling Alleviates Symptoms of Attention Deficit Hyperactivity Disorder via Anti-Inflammatory Effects in Spontaneous Hypertensive Rats

“…Activated microglia are usually marked by Iba1, and GFAP is used to mark astrocytes. According to our previous research, mast cell-mediated neuroinflammation play a role in ADHD while the interaction between glia and mast cells may aggravate inflammatory responses in ADHD ( Song et al, 2020 ). Toluidine blue is often used to evaluate the expression of mast cells, and tryptase is secreted from activated mast cells ( Irani and Schwartz, 1994 ).…”

“…Besides, peripheral inflammation could generate several pro-inflammatory and neurotoxic mediators, causing neuroinflammation through the MAPK and NF-κB pathways ( Kempuraj et al, 2017 ). We also proposed that ADHD may be a neuroinflammatory disease, related to the activation of immune cells in the brain based on literature review ( Song et al, 2020b ).…”

Histamine, Neuroinflammation and Neurodevelopment: A Review

“…Given their numerous cellular interactions and their role in neuroinflammation, it has been postulated that brain mast cells may be implicated in NDDs such as ASD (Theoharides et al, 2013) and ADHD (Song et al, 2020) but further roles in the etiology of NDDs remain unclear. The association with ASD is suggested by findings of mast cell related markers such as elevated serum neurotensin (Carraway et al, 1982;Alysandratos et al, 2012;Tsilioni et al, 2014), proinflammatory cytokines (Li et al, 2009) and the chemoattractant, monocyte chemoattractant protein-1 (MCP-1) (Vargas et al, 2005) in brain parenchyma and cerebrospinal fluid in patients with ASD.…”

“…The association with ASD is suggested by findings of mast cell related markers such as elevated serum neurotensin (Carraway et al, 1982;Alysandratos et al, 2012;Tsilioni et al, 2014), proinflammatory cytokines (Li et al, 2009) and the chemoattractant, monocyte chemoattractant protein-1 (MCP-1) (Vargas et al, 2005) in brain parenchyma and cerebrospinal fluid in patients with ASD. Secondly, ADHD has been commonly seen alongside allergic, inflammatory and autoimmune diseases (Song et al, 2020) and children with atopic eczema may be more susceptible to developing ADHD (Genuneit et al, 2014). This, along with the previously discussed associations between ADHD and neuroinflammation, has led to interest in mast cells as an important mediator of this (Song et al, 2020).…”

“…Secondly, ADHD has been commonly seen alongside allergic, inflammatory and autoimmune diseases (Song et al, 2020) and children with atopic eczema may be more susceptible to developing ADHD (Genuneit et al, 2014). This, along with the previously discussed associations between ADHD and neuroinflammation, has led to interest in mast cells as an important mediator of this (Song et al, 2020). However, to our knowledge, there are no studies that have investigated the potential role, if any, of mast cells in ADHD specifically.…”