Attention deficit hyperactivity disorder (ADHD) is a childhood-onset chronic neurobehavioral disorder, with multiple genetic and environmental risk factors. Chronic inflammation may be critical for the progression of ADHD. An Shen Ding Zhi Ling (ASDZL) decoction, a traditional Chinese medicine prescription, is clinically used in ADHD treatment. In this study, we investigated the effects and underlying anti-inflammatory mechanisms of ASDZL in young spontaneously hypertensive rats (SHRs), a widely used model of ADHD. SHRs were divided into the SHR model group (vehicle), atomoxetine group (4.56 mg/kg/day) and ASDZL group (21.25 g/kg/day), and orally administered for four weeks. Wistar Kyoto rats were used as controls (vehicle). We found that ASDZL significantly controlled hyperactivity and impulsivity, and improved spatial memory of SHRs in the open field test and Morris water maze test. ASDZL reduced the pro-inflammatory factors interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 and increased anti-inflammatory factor IL-10 in SHRs, and decreased the activation of microglia, astrocytes and mast cells in the prefrontal cortex (PFC) and hippocampus. Furthermore, the results indicated that ASDZL inhibited the neuroinflammatory response by protecting the integrity of the blood-brain barrier and suppressing the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways of SHRs. In conclusion, these findings revealed that ASDZL attenuated ADHD symptoms in SHRs by reducing neuroinflammation.
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.
Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder. It may impact the cognitive and social functions throughout childhood and determine adult outcomes. Dopamine (DA) deficiency theory is the pathogenesis of ADHD that is recognized by most international literature. Existing studies have shown that DA deficiency is caused by the abnormal function of the DA transporter and an imbalance in the DA receptor functionality. Recent clinical and experimental studies have found that the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway acts a pivotal part in DA vesicle circulation and ADHD pathogenesis. An Shen Ding Zhi Ling (ASDZL) is a traditional Chinese medicine (TCM) prescription, which was widely prescribed to treat ADHD in Jiangsu, China, but its therapeutic mechanism is unclear. Therefore, we constructed a spontaneously hypertensive rat (SHR) model to explain its mechanism. SHRs were randomly assigned to four groups: SHR model group (vehicle), methylphenidate hydrochloride group (MPH), ASDZL group, and 7,8-dihydroxyflavone group (7,8-DHF). At the same time, the above groups were given continuous medication for four weeks. The results show that ASDZL, MPH, and 7,8-DHF group could significantly improve the spatial memory of SHRs in the Morris water maze tests. ASDZL increased the levels of BDNF, TrkB, p75 neurotrophin receptor (p75), C-Jun N-terminal kinases 1 (JNK1), and nuclear factor kappa B (NF-κB) in the prefrontal cortex (PFC) and hippocampus synaptosome of SHRs. The results of this study suggest that ASDZL can relieve the symptoms of ADHD in SHRs by regulating the balance between the BDNF/TrkB signaling pathway (promoting vesicle circulation) and the BDNF/P75/JNK1/NF-κB signaling pathway (inhibiting vesicle circulation) within the PFC and hippocampus synaptosome to increase the DA concentration in the synaptic cleft. The BDNF/TrkB signal pathway within the PFC and hippocampus synaptosome was activated by 7,8-DHF to increase DA concentration in the synaptic cleft. Whether 7,8-DHF can activate or inhibit the BDNF/P75 signaling pathway remains unclear.
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