Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non‐Alzheimer's Type

Bettendorff, Lucien; Mastrogiacomo, Frank; Wins, Pierre; Kish, Stephen J.; Grisar, Thierry; Ball, Melvyn J.

doi:10.1046/j.1471-4159.1997.69052005.x

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…Such a mechanism could help to better understand the events involved in the onset of neurodegenerative diseases (64). It is therefore interesting to point out that thiamine deficiency has been shown to exacerbate the pathology of Alzheimer disease (63,65,66) and that there are dysfunctions of thiamine metabolism in neurodegenerative diseases (67,68).…”

Section: Synthesis Accumulation and Hydrolysis Of Thtp In Differentmentioning

confidence: 99%

Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain

Gangolf

Wins

Thiry

et al. 2010

Journal of Biological Chemistry

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In animals, thiamine deficiency leads to specific brain lesions, generally attributed to decreased levels of thiamine diphosphate, an essential cofactor in brain energy metabolism. However, another far less abundant derivative, thiamine triphosphate (ThTP), may also have a neuronal function. Here, we show that in the rat brain, ThTP is essentially present and synthesized in mitochondria. In mitochondrial preparations from brain (but not liver), ThTP can be produced from thiamine diphosphate and P i . This endergonic process is coupled to the oxidation of succinate or NADH through the respiratory chain but cannot be energized by ATP hydrolysis. ThTP synthesis is strongly inhibited by respiratory chain inhibitors, such as myxothiazol and inhibitors of the H ؉ channel of Thiamine (vitamin B1) is essential for brain function, and its deficiency causes specific brain lesions (1, 2). It is thought that this selective vulnerability results from decreased levels of thiamine diphosphate (ThDP), 3 an indispensable cofactor for several key enzymes in cell energy metabolism (especially pyruvate and oxoglutarate dehydrogenases and transketolase).

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Section: Synthesis Accumulation and Hydrolysis Of Thtp In Differentmentioning

confidence: 99%

Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain

Gangolf

Wins

Thiry

et al. 2010

Journal of Biological Chemistry

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“…While one study reported normal total blood thiamine levels in patients with Alzheimer's dementia [15], others showed decreased levels in plasma or erythrocytes [16], [17]. ThDP levels are decreased in postmortem brains of patients with Alzheimer's disease [18], [19] and frontal lobe degeneration of the non-Alzheimer's type [20].…”

Section: Introductionmentioning

confidence: 99%

Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

et al. 2010

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BackgroundThiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines.Methodology and Principal FindingsThiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines.Conclusions and SignificanceThe high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.

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“…Methylphenidate has been studied as an adjuvant medication for the treatment of depression and apathy in various disorders (Marin et al, 1995; Chatterjee and Fahn, 2002). Analyses of the neurochemical correlates of FTD based on autopsy tissue have generally implicated deficits in DA and NA neurotransmission (Bettendorff et al, 1997; Francis et al, 1993; Gilbert et al, 1988; Nagaoka et al, 1995; Sjogren et al, 1998; Sparks and Markesbery, 1991). For example, Sjogren et al (1998) reported a significant reduction in the CSF concentration of homovanillic acid, a major metabolite of DA, in a large sample of frontotemporal dementia cases.…”

Section: Introductionmentioning

confidence: 99%

Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia

Rahman

Robbins

Hodges

et al. 2005

Neuropsychopharmacol

119

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The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, doubleblind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decisionmaking behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

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Low Thiamine Diphosphate Levels in Brains of Patients with Frontal Lobe Degeneration of the Non‐Alzheimer's Type

Cited by 12 publications

References 26 publications

Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain

Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain

Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia

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