A Double-edged Sword: Uric Acid and Neurological Disorders

Pu, Fang; Li, Xinyuan; Luo, Jin; Wang, Hong; Yang, Xiaofeng

doi:10.4172/2168-975x.1000109

Cited by 45 publications

(37 citation statements)

References 32 publications

(33 reference statements)

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“…This includes, notably, uric acid and carnosine, which are known to be antioxidants and neuroprotective agents (Fang, et al, 2013; Bae, et al, 2013;). This regional specificity may be linked to surveillance responses, which serve to reduce oxidative stress and protect against oxidative damage.…”

Section: Resultsmentioning

confidence: 99%

Brain Region Mapping Using Global Metabolomics

Ivanišević¹,

Epstein²,

Kurczy³

et al. 2014

Chemistry & Biology

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SUMMARY Historically, studies of brain metabolism have been based on targeted analyses of a limited number of metabolites. Here we present a novel untargeted mass spectrometry-based metabolomics approach that has successfully uncovered differences in broad array of metabolites across anatomical regions of the mouse brain. The NSG immunodeficient mouse model was chosen because of its ability to undergo humanization leading to numerous applications in oncology and infectious disease research. Metabolic phenotyping by hydrophilic interaction liquid chromatography and nanostructure imaging mass spectrometry revealed unique water-soluble and lipid metabolite patterns between brain regions. Neurochemical differences in metabolic phenotypes were mainly defined by various phospholipids and several intriguing metabolites including carnosine, cholesterol sulfate, lipoamino acids, uric and sialic acid whose physiological roles in brain metabolism are poorly understood. This study lays important groundwork by defining regional homeostasis for the normal mouse brain to give context to the reaction to pathological events.

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Section: Resultsmentioning

confidence: 99%

Brain Region Mapping Using Global Metabolomics

Ivanišević¹,

Epstein²,

Kurczy³

et al. 2014

Chemistry & Biology

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“…Uric acid has been linked with a variety of psychological conditions, including neurodegenerative conditions and emotion-related psychopathology (Albert et al, 2015; Bowman et al, 2010; Fang et al, 2013; Jahangard et al, 2014; Kesebir et al, 2014; Lyngdoh et al, 2013; Machado-Vieira et al, 2008). Although variations in uric acid level alters neural transmission (Ortiz et al, 2015; Ozten et al, 2015), the brain functions that link uric acid and mental health have yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have suggested mechanisms by which increased uric acid levels may alter brain function (Alvarez-Lario & Macarron-Vicente, 2011; Fang et al, 2013; Ortiz et al, 2015). Uric acid is considered a neuroprotective factor against oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

“…For example, increased uric acid levels accelerate purine transformation, leading to alterations of neural transmission (Ortiz et al, 2015; Ozten et al, 2015). Additionally, uric acid has been linked with neurodegenerative conditions, such as Alzheimer’s, Parkinson’s, and Huntington’s disease, as well as Multiple Sclerosis and mild cognitive impairment (MCI) associated with aging (Bowman et al, 2010; Fang et al, 2013). The role of uric acid in mental health is also an emerging area of research.…”

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confidence: 99%

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The hippocampal response to psychosocial stress varies with salivary uric acid level

et al. 2016

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Uric acid is a naturally occurring, endogenous compound that impacts mental health. In particular, uric acid levels are associated with emotion-related psychopathology (e.g., anxiety and depression). Therefore, understanding uric acid’s impact on the brain would provide valuable new knowledge regarding neural mechanisms that mediate the relationship between uric acid and mental health. Brain regions including the prefrontal cortex, amygdala, and hippocampus underlie stress reactivity and emotion regulation. Thus, uric acid may impact emotion by modifying the function of these brain regions. The present study used functional magnetic resonance imaging (fMRI) during a psychosocial stress task to investigate the relationship between baseline uric acid levels (in saliva) and brain function. Results demonstrate that activity within the bilateral hippocampal complex varied with uric acid concentrations. Specifically, activity within the hippocampus and surrounding cortex increased as a function of uric acid level. The current findings suggest that uric acid levels modulate stress-related hippocampal activity. Given that the hippocampus has been implicated in emotion regulation during psychosocial stress, the present findings offer a potential mechanism by which uric acid impacts mental health.

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“…Low uric acid levels have been linked to several inflammatory and degenerative diseases, such as acute graft-versus-host disease [38] and neurological diseases, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, and multiple sclerosis [39]. These associations have been attributed to the reduced antioxidative capacity associated with hypourisemia [38,39]. …”

Section: Discussionmentioning

confidence: 99%

Association between Hypouricemia and Reduced Kidney Function: A Cross-Sectional Population-Based Study in Japan

Wakasugi¹,

Kazama²,

Narita³

et al. 2015

Am J Nephrol

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Background: Hypouricemia, conventionally defined as a serum uric acid level of ≤2 mg/dl, is considered a biochemical disorder with no clinical significance. However, individuals with renal hypouricemia have a high risk of urolithiasis and exercise-induced acute kidney injury, both of which are risk factors for reduced kidney function. Methods: To test the hypothesis that individuals with hypouricemia would be at a higher risk of reduced kidney function, we conducted a population-based cross-sectional study using data from the Specific Health Checkups and Guidance System in Japan. Logistic analysis was used to examine the relationship between hypouricemia and reduced kidney function, defined as estimated glomerular filtration rate <60 ml/min/1.73 m². Results: Among 90,710 men (mean age, 63.8 years) and 136,935 women (63.7 years), 193 (0.2%) and 540 (0.4%) were identified as having hypouricemia, respectively. The prevalence of hypouricemia decreased with age in women (p for trend <0.001), but not in men (p for trend = 0.24). Hypouricemia was associated with reduced kidney function in men (odds ratio, 1.83; 95% confidence interval, 1.23-2.74), but not in women (0.61; 0.43-0.86), relative to the reference category (i.e., serum uric acid levels of 4.1-5.0 mg/dl) after adjusting for age, drinking, smoking, diabetes, hypertension, hypercholesterolemia, obesity, and history of renal failure. Sensitivity analyses stratified by diabetic status yielded similar results. Conclusions: This study is the first to provide evidence that hypouricemia is associated with reduced kidney function in men. Further research will be needed to determine the long-term prognosis of individuals with hypouricemia.

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A Double-edged Sword: Uric Acid and Neurological Disorders

Cited by 45 publications

References 32 publications

Brain Region Mapping Using Global Metabolomics

Brain Region Mapping Using Global Metabolomics

The hippocampal response to psychosocial stress varies with salivary uric acid level

Association between Hypouricemia and Reduced Kidney Function: A Cross-Sectional Population-Based Study in Japan

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