Cerebrospinal fluid concentrations of large neutral and basic amino acids in Macaca mulatta: diurnal variations and responses to chronic changes in dietary protein intake

Grimes, Michael; Cameron, Judy L.; Fernstrom, John D.

doi:10.1016/j.metabol.2008.08.015

Cited by 13 publications

(6 citation statements)

References 56 publications

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“…Another group indicated that there was no statistically significant difference in serine concentration between the CSF of patients with AD and that of controls [ 14 , 45 ]. However, these studies were performed with relatively small sample sizes and amino acids concentration in the CSF seemingly influenced by the content of daily diet [ 46 ], further studies with larger sample sizes are needed to elucidate the relations between serine concentration in the CSF and AD.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

et al. 2018

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BackgroundAlzheimer’s disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles.MethodsWe performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch’s t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis.ResultsWe found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH.ConclusionsThis study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.Electronic supplementary materialThe online version of this article (10.1186/s40364-018-0119-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

et al. 2018

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“…Although direct measures of tryptophan influx into the human brain are currently not possible, the effectiveness of these challenges has been demonstrated by several animal studies (Biskup et al, 2012;Grimes, Cameron, & Fernstrom, 2000;Lieben, Blokland, Westerink, & Deutz,, 2004) and indirect measures of 5-HT levels in humans (e.g., CSF; Williams, Shoaf, Hommer, Rawlings, & Linnoila, 1999;Young & Gauthier, 1981). These interventions reduce or enhance the availability of the essential amino acid tryptophan, the dietary precursor of 5-HT in the brain, and thus help to investigate the role of the serotonergic system in the modulation of cognitive functions and mood among others (Lindseth, Helland, & Caspers, 2015;Silber & Schmitt, 2010).…”

Section: Introductionmentioning

confidence: 99%

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

Deza‐Araujo

Neukam

Marxen

et al. 2018

Human Brain Mapping

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It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double‐blind, randomized, cross‐over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting‐state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion‐related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.

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“…Because all 3 monoamines--DA, NE, and 5HT-- show marked age-related changes across the first year of life in the monkey, and are known to be sensitive to both experimental manipulations of diet and the early rearing environment (Goldman-Rackic & MacBrown, 1982; Grimes, Cameron, & Fernstrom, 2000; Higley, Suomi, & Linnoila, 1992; Maestripieri, Higley, Lindell, Newman, McCormack, & Sanchez, 2006), the specific question was whether the monoamine activity would be most affected during or subsequent to the period of ID Several reports in rodent models had indicated the effects of ID on the brain linger after the anemia has resolved, and there may even be a compensatory response following recovery (Dallman and Spirito, 1977). Severe ID generally lowers DA concentrations and reduces transporter and receptor levels in the rat brain, but a more moderate ID that is corrected in early lactation causes an up-regulation of DA activity in association with increased transferrin receptors and iron transporters in the brain (Beard, Felt, Schallert, Burhas, Connor, & Georgieff, 2006; Felt, Beard, Schallert, Shao, Aldridge, Connor, Georgieff, & Lozoff, 2006).…”

Section: Introductionmentioning

confidence: 99%

A history of iron deficiency anemia during infancy alters brain monoamine activity later in juvenile monkeys

Coe

Lubach

Bianco

et al. 2009

Developmental Psychobiology

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Both during and after a period of iron deficiency (ID), iron-dependent neural processes are affected, which raises the potential concern that the anemia commonly experienced by many growing infants could have a protracted effect on the developing brain. To further investigate the effects of ID on the immature brain, 49 infant rhesus monkeys were evaluated across the first year of life. The mothers, and subsequently the infants after weaning, were maintained on a standardized diet containing 180 mg/kg of iron and were not provided other iron-rich foods as treats or supplements. As the infants grew, they were all screened with hematological tests, which documented that 16 (33.3%) became markedly ID between 4-to-8 months of age. During this anemic period and subsequently at one year of age, cerebrospinal fluid (CSF) specimens were collected to compare monoamine activity in the ID and iron-sufficient infants. Monoamine neurotransmitters and metabolite levels were normal at 4 and 8 months of age, but by one year the formerly anemic monkeys had significantly lower dopamine and significantly higher norepinephrine levels. These findings indicate that ID can affect the developmental trajectory of these two important neurotransmitter systems, which are associated with emotionality and behavioral performance, and further that the impact in the young monkey was most evident during the period of recovery.

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Cerebrospinal fluid concentrations of large neutral and basic amino acids in Macaca mulatta: diurnal variations and responses to chronic changes in dietary protein intake

Cited by 13 publications

References 56 publications

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Comparative analysis of cerebrospinal fluid metabolites in Alzheimer’s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

A history of iron deficiency anemia during infancy alters brain monoamine activity later in juvenile monkeys

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