Effects of biotin deficiency on short term memory: The role of glutamate, glutamic acid, dopamine and protein kinase A

Munzuroğlu, Mustafa; Danisman, Betul; Akçay, Güven; Yelli, İhsan; Aslan, Mutay; Derın, Narin

doi:10.1016/j.brainres.2022.148031

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…Previous studies have implicated that biotin deficiency can cause locomotor deficits and mitochondrial pathology in a tau-toxicity model (14). Such biotin deficiency in rats also leads to short-term memory loss and deteriorated locomotor activity, further suggesting a role of B-vitamin biotin in PD (27). Gut microbiota is known to mediate B vitamin bioavailability; a recent study showed that prebiotic supplementation increases the abundance of biotin-producing gut bacteria, particularly Bacteroides spp., in a high-fat diet mouse model (13).…”

Section: Discussionmentioning

confidence: 99%

“…Biotin, or vitamin B 7 , is a water-soluble essential vitamin either obtained through diet or produced by the gut microbiome (13). Biotin acts as a critical cofactor for various carboxylases involved in a range of metabolic processes, including dopamine production (27). Previous studies have implicated that biotin deficiency can cause locomotor deficits and mitochondrial pathology in a tau-toxicity model (14).…”

Section: Discussionmentioning

confidence: 99%

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Biotin rescues manganese-induced Parkinson’s disease phenotypes and neurotoxicity

Lai,

Reina-Gonzalez,

Maor

et al. 2023

Preprint

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Occupational exposure to manganese (Mn) induces manganism and has been widely linked as a contributing environmental factor to Parkinson’s disease (PD), featuring dramatic signature overlaps between the two in motor symptoms and clinical hallmarks. However, the molecular mechanism underlying such link remains elusive, and for combating PD, effective mechanism-based therapies are lacking. Here, we developed an adultDrosophilamodel of Mn toxicity to recapitulate key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosome and mitochondria. We performed global metabolomics on flies at an early stage of toxicity and identified metabolism of the B vitamin, biotin (vitamin B7), as a master pathway underpinning Mn toxicity with systemic, body–brain increases in Mn-treated groups compared to the controls. Using BtndRNAimutant flies, we show that biotin depletion exacerbates Mn-induced neurotoxicity, parkinsonism, and mitochondrial dysfunction; while in Mn-exposed wild-type flies, biotin feeding dramatically ameliorates these pathophenotypes. We further show in human induced stem cells (iPSCs)- differentiated midbrain dopaminergic neurons that the supplemented biotin protects against Mn-induced neuronal loss, cytotoxicity, and mitochondrial dysregulation. Finally, human data profiling biotin-related proteins show for PD cases elevated circulating levels of biotin transporters but not of metabolic enzymes compared to healthy controls, suggesting humoral biotin transport as a key event involved in PD. Taken together, our findings identified compensatory biotin pathway as a convergent, systemic driver of Mn toxicity and parkinsonian pathology, providing new basis for devising effective countermeasures against manganism and PD.Significance StatementEnvironmental exposure to manganese (Mn) may increase the risk for Parkinson’s disease (PD); however, the mechanistic basis linking the two remains unclear. Our adult fruit fly (Drosophila) model of Mn toxicity recapitulated key Parkinson’s hallmarksin vivospanning behavioral deficits, neuronal loss, and mitochondrial dysfunction. Metabolomics identified the biotin (vitamin B7) pathway as a key mediator, featuring systemic biotin increases in the flies. Rescue trials leveraging biotin-deficient flies, wild-type flies, and human iPSC-derived dopaminergic neurons determined biotin as a driver of manganism, with the parkinsonian phenotypes dramatically reversed through biotin supplementation. Our findings, in line with overexpressed circulating biotin transporters observed in PD patients, suggest compensatory biotin pathway as a key to untangle the Mn-PD link for combating neurodegenerative disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biotin rescues manganese-induced Parkinson’s disease phenotypes and neurotoxicity

Lai,

Reina-Gonzalez,

Maor

et al. 2023

Preprint

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The impact of magnesium biotinate and arginine silicate complexes on metabolic dysfunctions, antioxidant activity, inflammation, and neuromodulation in high-fat diet-fed rats

Sahin,

Orhan

et al. 2024

Clin Exp Med

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Biotin and arginine play crucial roles in lipid metabolism and may offer promising interventions against obesity. This study examined the combined effect of magnesium biotinate (MgB) and inositol-stabilized arginine silicate complex (ASI) on obesity-related oxidative imbalance, inflammation, lipid metabolism and neuromodulation in rats on a high-fat diet (HFD). Forty rats were divided into five groups: (a) control: rats were fed a standard diet containing 12% of energy from fat; (b) HFD: rats were fed the HFD with 42% of energy from fat; (c) HFD + MgB: rats were fed the HFD and given 0.31 mg/kg body weight (BW) MgB, (d) HFD + ASI: rats were fed the HFD and were given 12.91 mg/kg BW ASI), and (e) HFD + MgB + ASI: rats were fed the HFD and given 0.31 mg/kg BW MgB and 12.91 mg/kg BW ASI). The combined administration of MgB and ASI reduced the levels of serum cholesterol, free fatty acid (FFA), and malondialdehyde (MDA), as well as liver inflammatory cytokines, sterol regulatory element-binding protein 1-c (SREBP-1c), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) proteins ( P < 0.001) compared to HFD rats without supplementation. Moreover, this combination increased the activities of antioxidant enzymes ( P < 0.05) and boosted the brain-derived neurotrophic factor (BDNF), serotonin, dopamine ( P < 0.001), as well as liver insulin receptor substrate 1 (IRS-1) and peroxisome proliferator-activated receptor gamma (PPAR-γ) ( P < 0.001). These findings suggest that combining MgB and ASI could deter liver fat accumulation and enhance lipid metabolism in HFD-fed rats by modulating various metabolic pathways and neuromodulators related to energy metabolism. This combination demonstrates potential in addressing obesity and its related metabolic dysfunctions .

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The Role of Catecholamines in the Pathogenesis of Diseases and the Modified Electrodes for Electrochemical Detection of Catecholamines: A Review

Zhang,

Wang,

Jiang

et al. 2024

Critical Reviews in Analytical Chemistry

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Effects of biotin deficiency on short term memory: The role of glutamate, glutamic acid, dopamine and protein kinase A

Cited by 4 publications

References 48 publications

Biotin rescues manganese-induced Parkinson’s disease phenotypes and neurotoxicity

Biotin rescues manganese-induced Parkinson’s disease phenotypes and neurotoxicity

The impact of magnesium biotinate and arginine silicate complexes on metabolic dysfunctions, antioxidant activity, inflammation, and neuromodulation in high-fat diet-fed rats

The Role of Catecholamines in the Pathogenesis of Diseases and the Modified Electrodes for Electrochemical Detection of Catecholamines: A Review

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