# The Influence of Serum Uric Acid on the Brain and Cognitive Dysfunction

**Authors:** Natasa R. Mijailovic, Katarina Vesic, Milica M. Borovcanin

PMC · DOI: 10.3389/fpsyt.2022.828476 · 2022-04-22

## TL;DR

This paper explores how uric acid in the blood may both protect and harm brain function, potentially affecting cognitive abilities through antioxidant and inflammatory effects.

## Contribution

The study provides a comprehensive overview of uric acid's dual role in cognitive functioning through oxidative stress and inflammation.

## Key findings

- Uric acid may have neuroprotective effects due to its antioxidant properties.
- Elevated uric acid levels could contribute to cognitive dysfunction via inflammatory processes.
- Gender differences may influence the impact of uric acid on cognitive health.

## Abstract

Uric acid is commonly known for its bad reputation. However, it has been shown that uric acid may be actively involved in neurotoxicity and/or neuroprotection. These effects could be caused by oxidative stress or inflammatory processes localized in the central nervous system, but also by other somatic diseases or systemic conditions. Our interest was to summarize and link the current data on the possible role of uric acid in cognitive functioning. We also focused on the two putative molecular mechanisms related to the pathological effects of uric acid—oxidative stress and inflammatory processes. The hippocampus is a prominent anatomic localization included in expressing uric acid's potential impact on cognitive functioning. In neurodegenerative and mental disorders, uric acid could be involved in a variety of ways in etiopathogenesis and clinical presentation. Hyperuricemia is non-specifically observed more frequently in the general population and after various somatic illnesses. There is increasing evidence to support the hypothesis that hyperuricemia may be beneficial for cognitive functioning because of its antioxidant effects but may also be a potential risk factor for cognitive dysfunction, in part because of increased inflammatory activity. In this context, gender specificities must also be considered.

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], GDA (guanine deaminase) [NCBI Gene 9615] {aka CYPIN, GAH, GUANASE, NEDASIN}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PNP (purine nucleoside phosphorylase) [NCBI Gene 4860] {aka NP, PRO1837, PUNP}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}
- **Diseases:** hypouricemia (MESH:C537757), neuronal damage (MESH:D009410), poor learning and memory (MESH:D007859), MCI (MESH:D060825), locomotor dysfunction (MESH:D001523), vascular or mixed (MESH:D060085), MS (MESH:D009103), cardiovascular disease (MESH:D002318), toxicity (MESH:D064420), neuroinflammation (MESH:D000090862), psychosis (MESH:D011618), intracranial hypertension (MESH:D019586), decreased spatial learning and memory (MESH:D008569), AD (MESH:D000544), neurological dysfunctions (MESH:D009461), neurological diseases (MESH:D020271), neurotoxicity (MESH:D020258), EAE (MESH:D004681), ischaemia (MESH:D007511), Brain and Cognitive Dysfunction (MESH:D003072), ALS (MESH:D000690), transient ischaemic attack (MESH:D002546), amnesia (MESH:D000647), PD (MESH:D010300), Hyperuricemia (MESH:D033461), infarction (MESH:D007238), depression (MESH:D003866), cerebrovascular disease (MESH:D002561), ischaemic stroke (MESH:D002544), Post-stroke (MESH:D020521), necrosis (MESH:D009336), Neurodegeneration (MESH:D019636), BBB impairment (MESH:C536830), diseases of civilization (MESH:D004194), metabolic syndrome (MESH:D024821), SCI (MESH:D013119), dementia (MESH:D003704), heart failure (MESH:D006333), Hippocampal dysfunction (MESH:D001927), vascular pathology (MESH:D005598), CNS diseases (MESH:D002493), hypoxia (MESH:D000860), gout (MESH:D006073), pneumococcal meningitis (MESH:D008586), MB (OMIM:613675), gliosis (MESH:D005911), ischemic neuronal injury (MESH:D017202), schizophrenia (MESH:D012559), VaD (MESH:D015140), HD (MESH:D006816), obesity (MESH:D009765), white matter atrophy (MESH:D000090122), Inflammation (MESH:D007249), cerebral ischemia (MESH:D002545), Neurological impairment (MESH:D009422), NM (MESH:C536816), endothelial dysfunction (MESH:D014652), CKD (MESH:D051436), UA (MESH:D011015), delirium (MESH:D003693)
- **Chemicals:** Xanthine (MESH:D019820), glutamate (MESH:D018698), allopurinol (MESH:D000493), O (MESH:D010100), Cu+ (MESH:D003300), Peroxynitrite (MESH:D030421), NO2 (MESH:D009585), caffeine (MESH:D002110), GMP (-), hydroxyl radicals (MESH:D017665), unsaturated fatty acids (MESH:D005231), CO (MESH:D002248), purines (MESH:D011687), superoxide anion (MESH:D013481), ATP (MESH:D000255), Hypoxanthine (MESH:D019271), H2O2 (MESH:D006861), nitrotyrosine (MESH:C002744), NO (MESH:D009569), guanine (MESH:D006147), calcium (MESH:D002118), singlet oxygen (MESH:D026082), lithium (MESH:D008094), guanosine (MESH:D006151), lipid (MESH:D008055), free radical (MESH:D005609), adenine (MESH:D000225), inosine (MESH:D007288), UA (MESH:D014527), ROS (MESH:D017382), CO2 (MESH:D002245), purine (MESH:C030985), peroxyl radicals (MESH:C049375), AMP (MESH:D000249)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC9072620/full.md

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Source: https://tomesphere.com/paper/PMC9072620