<i>N</i>‐Acetyl‐Aspartyl‐Glutamate: Regional Levels in Rat Brain and the Effects of Brain Lesions as Determined by a New HPLC Method

Koller, Kerry J.; Zaczek, Robert; Coyle, Joseph T.

doi:10.1111/j.1471-4159.1984.tb12854.x

Cited by 337 publications

(141 citation statements)

References 26 publications

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“…Post hoc pairwise comparisons by t-test revealed significantly different NAA (po0.05) in the following areas: auditory cortex higher than all others; dorsal hippocampus, cingulate and mediofrontal cortex higher than the remaining regions; and ventral hippocampus, amygdala, and accumbens higher than striatum, which was the region with the lowest NAA level. These higher concentrations in cortex and lowest in striatum are consistent with the previous rat studies (Koller et al, 1984;Florian et al, 1996, Bustillo et al, 2004. Factorial ANOVAs also failed to document a drug main effect or interaction (p40.05) for the other metabolites measured: alanine, aspartate, betaine, PEA, choline, glutamine, GPC, lactate, NAAG, succinate, taurine, GABA, glycine, glutamate, GSH, inositol, phospho choline, and creatinine total.…”

Section: Resultssupporting

confidence: 77%

Long-Term Treatment of Rats with Haloperidol: Lack of an Effect on Brain N-Acetyl Aspartate Levels

Bustillo

Barrow

Paz

et al. 2005

Neuropsychopharmacol

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Proton magnetic resonance spectroscopy ( 1 H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in rat the effect of haloperidol on NAA, glutamate, and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Two groups of 16 rats each were treated with haloperidol depo (38 mg/kg/month) and vehicle for 6 months and were killed. Concentrations of metabolites were determined by high-resolution magic angle proton magnetic resonance spectroscopy (HR-MAS 1 H-MRS) at 11.7 T in ex-vivo punch biopsies from the following brain regions: medial frontal and cingulate cortex, striatum, nucleus accumbens, dorsal and ventral hippocampus, amygdala, and temporal cortex. Factorial ANOVA of NAA concentrations revealed no significant effect of drug group (F(1,212) ¼ 1.5; p ¼ 0.22) or a group by brain region interaction (F(7,212) ¼ 1.0; p ¼ 0.43). There was a significant main effect of region (F(7,212) ¼ 17.8; po0.001) with lower NAA in the striatum. A prolonged exposure to the dopamine D2 receptor blockade effects of haloperidol does not result in changes in NAA, glutamate, glutamine, and other metabolites in the proton spectrum. These results are consistent with the only other two studies of the effect of antipsychotic drugs on NAA in the rat brain. The documented lower NAA in chronically treated schizophrenia patients is most likely not a simple effect of antipsychotic medications.

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Section: Resultssupporting

confidence: 77%

Long-Term Treatment of Rats with Haloperidol: Lack of an Effect on Brain N-Acetyl Aspartate Levels

Bustillo

Barrow

Paz

et al. 2005

Neuropsychopharmacol

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“…Beyin tümör dokusu ve beyin hücre kültür örneklerinde yapılan çalışmalarda NAA'nın sadece nöronal dokuyla sınırlı olduğu belirtilmiştir (42,43,44,45). Ayrıca spesifik nörotoksik ajanların neden olduğu lezyonlarda NAA düşüklüğü gösterilmiştir (46 Çalışmamızda serum serüloplazmin düzeyleri İPH grubunda sağlıklı kontroller ile karşılaştırıldığında anlamlı olarak daha düşüktü. Ayrıca İPH grubunda H-1 MRS verilerine bakıldığında (KL) NAA/ Cho düşüklüğü ile serum serüloplazmin düşüklüğü arasında pozitif korelasyon saptadık (Şekil 1).…”

Section: Discussionunclassified

The Role of Ceruloplasmin in Neurodegeneration in Parkinson’s Disease

Gürer¹,

Aydın²,

Gökçe³

et al. 2016

tnd

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Amaç: İdiyopatik Parkinson hastalığında (İPH) oksidatif stres nöronal hücre ölümü üzerinde majör role sahiptir. Serüloplazmin ferrooksidaz aktivitesi ile ferröz demiri ferrik forma okside eder ve böylece hücrenin DNA, lipid ve protein bileşenlerini oksidatif hasardan korur. Bizim çalışmamızda proton manyetik rezonans spektroskopi (H-1 MRS) ile serüloplazmin eksikliğinin nörodejenerasyon üzerindeki etkisi araştırılmıştır. Gereç ve Yöntem: İPH tanılı 23 hasta ve 12 sağlıklı kontrol olguda iki yanlı putamen tek voksel H-1 MRS yöntemiyle incelendi. Her iki grupta N-asetil aspartat (NAA), kreatin (Cr) ve kolin (Cho) pik değerleri ve serum serüloplazmin düzeyleri belirlendi. Bulgular: İPH hastalarında semptomatik ekstremitenin kontralateral (KL) putaminal bölge NAA/Cho ve NAA/Cr oranı kontrol grubuna kıyasla anlamlı derecede düşüktü. Ayrıca İPH grubunda KL NAA/Cho ve NAA/Cr oranları ipsilateraline (İL) göre anlamlı derecede düşüktü (p<0,001). Semptomatik ekstremitenin İL putaminal bölgeye ait metabolit oranları karşılaştırıldığında sağlıklı kontrol ile İPH grubu arasında anlamlı fark saptanmadı. Serum serüloplazmin seviyeleri kontrol grubu ile karşılaştırıldığında İPH grubunda anlamlı derecede düşük saptandı (p<0,001). İPH grubunda KL putaminal NAA/Cho oranı ile serüloplazmin seviyeleri arasında anlamlı korelasyon saptandı (p=0,011). Sonuç: Çalışmamızda saptanan serum serüloplazmin düşüklüğü ile KL putamen NAA/Cho oranı arasındaki bu korelasyon serbest radikal aracılı nöronal hücre ölümünde serüloplazmin yetersizliğinin katkıda bulunabileceği hipotezini desteklemektedir. Anahtar Kelimeler: İdiyopatik Parkinson hastalığı, proton manyetik rezonans spektroskopi, serüloplazmin Objective: Oxidative stress has been implicated to play a major role in the neuronal cell death in idiopathic Parkinson's disease (IPD). Ceruloplasmin is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form and thus helps prevent oxidative damage to proteins, lipids, and DNA. The aim of this study was to determine the serum ceruloplasmin levels in patients with IPD and evaluate its role in neurodegeneration using hydrogen proton magnetic resonance spectroscopic imaging (H-1 MRSI). Materials and Methods: Twenty-three patients with the IPD and 12 healthy controls were studied using single-voxel H-1 MRSI of the bilateral putamen. The peak ratios of N-acetyl aspartate (NAA) to creatinine (Cr) and choline (Cho) were measured in both groups and serum ceruloplasmin levels were detected. Results: Compared with the controls, the ratios of NAA/Cho and NAA/Cr in putamen contralateral (CL) to the symptomatic limbs were significantly lower in patients with IPD. Also in the IPD group, CL NAA/Cho and NAA/Cr ratios were significantly lower than the ipsilateral (IL) values (p<0.001). There was no significant difference between ratios of metabolites in putamen IL to the symptomatic limbs in the IPD group compared with the healthy controls. The mean serum ceruloplasmin level of IPD patients was significantly lower than that of the control group (...

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“…NAA was analysed by a method previously described by Urenjak et al (1993). Detection for NAAG was carried out using an Anachem SAX (46 mm internal diameter, 25 cm length) column fitted with a 1-cm guard column, according to Koller et al (1984).…”

Section: Hplc Analysis Of Metabolitesmentioning

confidence: 99%

Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy

Florian

Pietsch²,

Noble³

et al. 1997

Br J Cancer

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Summary Well-characterized cell lines established from primitive neuroectodermal tumours (PNETs) were examined by proton nuclear magnetic resonance ('H-NMR) spectroscopy and chromatographic analysis of perchloric acid extracts, following amplification in cell culture. A characteristic 'H-NMR spectroscopic metabolite pattern was found for medulloblastoma cell lines, which clearly discriminates these cells from PNETs of other locations in the central nervous system (CNS), on the basis of their N-acetyl aspartate (NM) and aspartate expression. Medulloblastoma cell lines were heterogeneous in respect of their metabolite expression, possibly owing to the heterogeneity in their differentiation along lineages of the CNS. All PNET spectra displayed similar features, including decreased NAA and creatine peaks and increased signals from choline compounds (Cho) compared with normal cerebellum. The expression of NM by the medulloblastoma lines was in the opposite order to the extent of neuronal differentiation, which may indicate their origin from a progenitor cell with the phenotype of an oligodendrocyte-type-2 astrocyte cell.Keywords: human primitive neuroectodermal tumour; human medulloblastoma; proton nuclear magnetic resonance spectroscopy; metabolite; cell line Primitive neuroectodermal tumours (PNETs) are highly malignant [grade IV according to the World Health Organization classification of brain tumours by Kleihues et al (1993)] and among the most common tumours of childhood. They are most frequently located in the cerebellum (i.e. cerebellar medulloblastomas), but tumours that have a similar appearance and biological behaviour have been found in other locations in the central nervous system (CNS), such as the cerebrum, pineal region or spinal cord. The nature and cell of origin of these tumours, composed of primitive or undifferentiated neuroepithelial cells, is controversial. Questions have been raised as to whether their cell of origin is unique to the portion of the CNS in which the tumour arises, or whether there is a primitive or undifferentiated cell common to all portions of the CNS. Rorke et al (1985) have suggested that these tumours arise from a single primitive multipotential cell that has the capacity to differentiate into one or more types of neural cellssuch as astrocytes, oligodendrocytes, neurons, ganglion cells or melanocytes -and are therefore regarded as malignant counterparts of multipotential neural progenitor cells.Progress in understanding the cell biology of these tumours has been hampered by the lack of cultured cell lines, since relatively few continuous medulloblastoma lines have been established thus far (Friedman et al, 1985;Jacobsen et al, 1985). However, the recent establishment of five new human PNET cell lines from surgical specimens (Pietsch et al, 1994) Correspondence to: S Williams investigate the biology, phenotype, lineage and metabolism of PNETs in detail. In the present study, metabolite profiles of several of these PNET cell lines in culture, together with two establishe...

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N‐Acetyl‐Aspartyl‐Glutamate: Regional Levels in Rat Brain and the Effects of Brain Lesions as Determined by a New HPLC Method

Cited by 337 publications

References 26 publications

Long-Term Treatment of Rats with Haloperidol: Lack of an Effect on Brain N-Acetyl Aspartate Levels

Long-Term Treatment of Rats with Haloperidol: Lack of an Effect on Brain N-Acetyl Aspartate Levels

The Role of Ceruloplasmin in Neurodegeneration in Parkinson’s Disease

Metabolic studies of human primitive neuroectodermal tumour cells by proton nuclear magnetic resonance spectroscopy

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