Changes in Free Amino Acids of Cerebrospinal Fluid and Plasma in Various Neurological Diseases

Iijima, Kunihiro; Takase, Sadao; Tsumuraya, Kenji; Endo, Minoru; Itahara, Katsuya

doi:10.1620/tjem.126.133

Cited by 20 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, plasma/CSF ratio of tyrosine concentrations was increased in MS patients (Iijima et al . ), while others found increased levels of tyrosine in CSF from MS patients (Qureshi and Baig ), results that were challenged in findings reporting that these amino acid changes are more related to unspecific changes in blood–CSF barrier (Garseth et al . ).…”

Section: Resultsmentioning

confidence: 96%

“…Despite the data presented here is based in exact massin some cases with an orthogonal approach with retention time with UHPLCwith all the limitations implicit in this (Jove et al 2011), we found that tyrosine metabolism, ubiquinone biosynthesis, b-alanine, nicotinate and nicotinamide and phenylalanine metabolism could be affected in MS. Furthermore, plasma/CSF ratio of tyrosine concentrations was increased in MS patients (Iijima et al 1978), while others found increased levels of tyrosine in CSF from MS patients (Qureshi and Baig 1988), results that were challenged in findings reporting that these amino acid changes are more related to unspecific changes in blood-CSF barrier (Garseth et al 2001). Furthermore, tyrosine levels were unchanged in plaques and white matter from MS patients (Langemann et al 1992).…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Gonzalo

Brieva

Tatzber

et al. 2012

Journal of Neurochemistry

View full text Add to dashboard Cite

Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-isoprostaglandin F2a is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor c (PPARc). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. Keywords: autoimmunity, lipid peroxidation, PPAR, protein oxidation. J. Neurochem. (2012) 123, 622-634. Multiple sclerosis is a complex pathology belonging to the group of chronic inflammatory autoimmune diseases. Several risk factors have been defined for this disease such as genetic pre-disposition, dietary and other environmental factors such as obesity and smoking habit (recently reviewed in (Young 2011). Patients suffering from this disease have a spectrum of clinical manifestations, generally episodic, with frequent intervals of exacerbations followed by periods of remission.The ethiopathogeny of this disease comprises many aspects of immune system with dysfunctionality, including dearranged cytokine profile, T-cell population imbalance, abnormal presence of altered B cell and inmunoglobins in CNS, inappropriate activation of natural killer, dendritic cells and Received March 6, 2012; revised manuscript received August 18, 2012; accepted August 19, 2012. Address correspondence and reprint requests to Dr Manuel Portero-Otin, Universidad de Lleida c/Montserrat Roig 2, 25008 Lleida, Spain. E-mail: manuel.portero@mex.udl.catAbbreviations used: 2-PY, N1-methyl-2-pyridone-5-carboxamide; 8-iso-PGF2a, 8-iso-prostaglandin F2a; CML, carboxymethyl-lysine; HODE, hydroxyoctadecadienoic acid; LC, liquid chromatography;...

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Gonzalo

Brieva

Tatzber

et al. 2012

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Different processes such as neuronal release and transport, glial uptake, diffusion barriers, sequestration in distinct metabolic pools, and degradation may be responsible for the modifications of glutamate levels in CSF. Nevertheless, various studies have demonstrated the existence of a blood-CSF barrier to amino acids and suggested that CSF glutamate concentrations should reflect its function within the central nervous system (McGale et al, 1977;Ijima et al, 1978;Kornhuber and Kornhuber, 1992;Rothstein et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

310

191

View full text Add to dashboard Cite

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (mmol/l) level was found to be significantly higher [F(1,31) ¼ 6.846, p ¼ 0.014] in OCD patients (47.1274.25) compared to control subjects (41.3673.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

show abstract

“…Interestingly, GLY had the greatest plasma-CSF ratio, 45.4 ± 19.6 (mean± s.d.) (Iijima et al, 1978). There were no statistically significant alterations in the GLY plasma-CSF ratio in patients with infectious diseases ( n = 60), spinal block ( n = 12), cerebrovascular disease ( n = 9), and degenerative diseases ( n = 57) (Iijima et al, 1978).…”

Section: Glycine Homeostasismentioning

confidence: 99%

“…(Iijima et al, 1978). There were no statistically significant alterations in the GLY plasma-CSF ratio in patients with infectious diseases ( n = 60), spinal block ( n = 12), cerebrovascular disease ( n = 9), and degenerative diseases ( n = 57) (Iijima et al, 1978). This suggests that factors distinct from the BBB may maintain homeostatic control over GLY plasma-CSF ratios.…”

Section: Glycine Homeostasismentioning

confidence: 99%