Research Article: Effects of taurine on resting-state fMRI activity in spontaneously hypertensive rats

Date Published: July 10, 2017

Publisher: Public Library of Science

Author(s): Vincent Chin-Hung Chen, Tsai-Ching Hsu, Li-Jeng Chen, Hong-Chun Chou, Jun-Cheng Weng, Bor-Show Tzang, Yi-Hsien Hsieh.

http://doi.org/10.1371/journal.pone.0181122

Abstract

Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

Partial Text

Attention deficit hyperactivity disorder (ADHD) is a very common developmental disorder in both children and adults worldwide, with prevalences of 5–10% [1] and 3–5% [2], respectively. Although the exact etiology of ADHD is still unclear, various causes of the pathogenesis of ADHD have been suggested. Inflammation has been associated with various neuropsychiatric illnesses, including ADHD. Elevated pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, CRP and tumor necrosis factor alpha (TNF-α), are known as common pathogenic parts of schizophrenia, ADHD and autism [3]. Children with extremely prematurely birth, recurrent, or persistently inflammation during the first 14 postnatal days are strongly associated with attention deficiency [4]. Accordingly, a systematic review article regarding inflammation among young people with neuropsychiatric diseases reveals that elevated inflammatory markers play critical roles in the development of ADHD [5].

Accumulating evidence suggests a strongly pathophysiological relationship between inflammation and attention-deficit hyperactivity disorder (ADHD) [5]. Elevated levels of pro-inflammatory cytokines such as interleukin (IL)-1 and C-reactive protein (CRP) are known to be diagnostic markers and crucial pathogenic factor of ADHD [3, 29–30]. When cell damage occurs, CRP binds to phosphocholine on cell membranes and promotes the binding of complements [31]. Evidence reveals that IL-1 has both neuromodulatory and neurodevelopmental functions that involve turnover neurotransmitters in various brain regions [32]. Interleukin-1 (IL-1α and IL-1β), IL-1Ra, and IL-1 receptors are found to be expressed in the brain [33]. Especially in relation to ADHD, IL-1β induces changes in dopamine (DA) and norepinephrine (NE) in the prefrontal cortex. Various studies have also shown that the systemic administration of IL-1β enhances DA and NE utilization in the prefrontal cortex (PFC) in both mice and rats [32, 34]. In this work, serum CRP and IL-1β levels were significantly lower in SHR rats that were administered a low dose or high dose of taurine. These results suggest that taurine can ameliorate inflammatory factors, resulting in ameliorating ADHD-like behaviors, such as hyperactivity, in SHR rats.

This study is the first to reveals the beneficial effects of taurine on an ADHD animal model. The treatment of SHR rats with a high dose of taurine significantly reduces the levels of pro-inflammatory cytokines and horizontal locomotor activity. Treatment with a low or high dose of taurine caused the FC of the bilateral hippocampus in SHR rats to return to the levels in rats of the WKY control group. Taurine significantly reduces the mALFF of bilateral hippocampus in SHR rats. Although no significant correlation was found between FC and horizontal activity or mALFF and horizontal activity, this study still disclosers the ameliorative effect of high-dose taurine on hyperactivity in SHR rats and suggests that taurine may be an alternative treatment for ADHD. However, further animal and clinical studies are required to determine the efficacy, safety, optimal dosage and precise mechanism of taurine for clinical purposes.

 

Source:

http://doi.org/10.1371/journal.pone.0181122

 

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