Department of Human Physiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, Warszawska Av, 30, 10-082, Olsztyn, Poland.
Department of Industrial and Food Microbiology, Faculty of Food Science, University of Warmia and Mazury in Olsztyn, Plac Cieszyński 1, 10-726, Olsztyn, Poland.
Psychopharmacology (Berl). 2019 Oct;236(10):2937-2958. doi: 10.1007/s00213-019-5180-0. Epub 2019 Feb 8.
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioural disorders with morphological and functional brain abnormalities. However, there is a growing body of evidence that abnormalities in the immune and endocrine systems may also account for the ADHD pathogenesis.
To test ADHD pathogenesis in neurological, immune and endocrine systems, this study examined the concentrations of cytokines, chemokines, oxidative stress markers, metabolic parameters, steroid hormones and steroidogenic enzymes in the serum and/or tissues of spontaneously hypertensive rats (SHRs, animal model of ADHD) and Wistar Kyoto rats (WKYs, control animals). Moreover, the volume of the medial prefrontal cortex (mPFC) as well as the density of dopamine 2 (D) receptor-expressing cells and tyrosine hydroxylase (TH)-positive nerve fibres in it was also elucidated.
Peripheral blood, spleen and adrenal gland samples, as well as brain sections collected on day 35 (juvenile) and day 70 (maturating) from SHRs and WKYs, were processed by ELISA and immunohistochemistry, respectively.
The results show significant increases of serum and/or tissue concentrations of cytokines, chemokines and oxidative stress markers in juvenile SHRs when compared to the age-matched WKYs. These increases were accompanied by a lowered volume of the mPFC and up-regulation of D in this brain region. In maturating SHRs, the levels of inflammatory and oxidative stress markers were normalised and accompanied by elevated contents of steroid hormones.
Significant elevations of serum and/or tissue contents of cytokines, chemokines and oxidative stress markers as well as volumetric and neurochemical alterations in the mPFC of juvenile SHRs may suggest the cooperation of neurological and immune systems in the ADHD pathogenesis. Elevated levels of steroid hormones in maturating SHRs may be a compensatory effect involved in reducing inflammation and ADHD symptoms.
注意力缺陷多动障碍（ADHD）是最常见的神经行为障碍之一，存在形态和功能脑异常。然而，越来越多的证据表明，免疫系统和内分泌系统的异常也可能导致 ADHD 的发病机制。
为了检验神经、免疫和内分泌系统中的 ADHD 发病机制，本研究检测了血清和/或组织中细胞因子、趋化因子、氧化应激标志物、代谢参数、类固醇激素和类固醇生成酶在自发性高血压大鼠（SHR，ADHD 动物模型）和 Wistar Kyoto 大鼠（WKY，对照动物）中的浓度。此外，还阐明了内侧前额叶皮质（mPFC）的体积以及其中多巴胺 2（D）受体表达细胞和酪氨酸羟化酶（TH）阳性神经纤维的密度。
分别通过 ELISA 和免疫组织化学方法处理来自 SHR 和 WKY 的外周血、脾和肾上腺组织样本以及脑切片。
与同龄的 WKY 相比，幼年 SHR 的血清和/或组织中细胞因子、趋化因子和氧化应激标志物的浓度显著增加。这些增加伴随着 mPFC 体积减小和该脑区 D 的上调。在成熟的 SHR 中，炎症和氧化应激标志物的水平恢复正常，并伴有类固醇激素含量升高。
幼年 SHR 的血清和/或组织中细胞因子、趋化因子和氧化应激标志物的含量升高，mPFC 的体积和神经化学改变，以及成熟 SHR 中类固醇激素水平升高，可能表明神经系统和免疫系统在 ADHD 发病机制中的协同作用。成熟 SHR 中类固醇激素水平升高可能是一种涉及减轻炎症和 ADHD 症状的代偿效应。
