Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects

Abstract  To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.     

Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Background:

Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS.

Methods:

Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects.

Results:

Significant reductions in N-acetylaspartate (NAA) and choline-containingCompound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group.

Conclusions:

Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.     

Decreased frontal lobe function in people with Internet addiction disorder

In our previous studies, we showed that frontal lobe and brainstem functions were abnormal in online game addicts. In this study, 14 students with Internet addiction disorder and 14 matched healthy controls underwent proton-magnetic resonance spectroscopy to measure cerebral function. Results demonstrated that the ratio of N-acetylaspartate to creatine decreased, but the ratio of cho- line-containing compounds to creatine increased in the bilateral frontal lobe white matter in people with Internet addiction disorder. However, these ratios were mostly unaltered in the brainstem, suggesting that frontal lobe function decreases in people with Internet addiction disorder.     

Hyperbaric oxygen therapy improves cognitive functioning after brain injury

Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hy- perbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney＇s free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats＇ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was sig- nificantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly im- proves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is me- diated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.     

首诊成人强迫症脑3D-多体素氢质子磁共振波谱分析

目的探讨强迫症（OCD）患者不同区域脑组织代谢特点。方法选择17例首诊未经治疗的成人OCD患者为研究对象,并以性别、年龄、受教育程度匹配的17例健康志愿者为对照组,采用3D-多体素氢质子磁共振波谱分析OCD患者前扣带回、中扣带回、左右额叶白质、左右丘脑和左右豆状核中大脑代谢物N-乙酰门冬氨酸（NAA）、胆碱（Cho）和肌酸（Cr）浓度变化,并分析NAA/Cr、Cho/Cr与OCD、焦虑和抑郁量表评分的相关性。结果OCD患者中扣带回的Cho/Cr明显低于对照组（P＜0.05）,左额叶白质Cho/Cr明显高于对照组（P＜0.05）;中扣带回NAA/Cr与焦虑量表评分呈正相关（r=0.712,P＜0.05）。结论OCD患者中扣带回Cho浓度减少、左额叶白质Cho浓度增高,可能是OCD的病理现象或代偿反应;中扣带回NAA/Cr与焦虑量表评分呈正相关。     

Posterior cingulate metabolic changes in frontotemporal lobar degeneration detected by magnetic resonance spectroscopy

Differences in prognosis and symptomatic treatment have highlighted the importance of the differential diagnosis of frontotemporal lobar degeneration (FTLD) and other dementias, but the variable clinical features make diagnosis difficult. We studied metabolic changes using multivoxel proton magnetic resonance spectroscopy (MRS) in regions of FTLD, including the posterior cingulate gyrus, which is also the area most affected by Alzheimers disease (AD) in the early stages. We examined six patients with FTLD, six with presumed AD, and five healthy volunteers using repetition and echo times of 2000 and 135 ms. We analysed peak ratios of choline (Cho), creatine (Cr), and N-acetylaspartate (NAA) from frontal and temporoparietal regions, basal ganglia, and posterior cingulate gyrus in both hemispheres. A decreased NAA/Cr ratio was observed in the posterior cingulate gyri in presumed AD (right: 1.56±0.44, P =0.011; left: 1.46±0.25, P =0.008) and FTD (right: 1.47±0.40, P =0.005; left: 1.36±0.32, P =0.002). No statistically significant changes in Cho/Cr were identified in the posterior cingulate gyri in presumed AD or FTLD, and no differences were observed in peak ratios in other regions. Decreased NAA may reflect neuronal activity in the posterior cingulate gyrus, and this study may contirbute to insights into the pathophysiology of FTLD.     

Proton magnetic resonance spectroscopy detects a relative decrease of N-acetylaspartate in the hippocampus of patients with dementia with Lewy bodies.

BACKGROUND AND PURPOSE: To characterize the cerebral metabolic changes in dementia with Lewy bodies patients. METHODS: The metabolic ratios of NAA/Cr and Cho/Cr in bilateral hippocampus were determined by proton magnetic resonance spectroscopy in 8 patients and 8 age-matched healthy controls. RESULTS: Dementia with Lewy bodies patients showed significantly lower NAA/Cr ratios in bilateral hippocampus, while the Cho/Cr ratio did not differ from the control group. CONCLUSIONS: Our data show relatively decrease of N-acetylaspartate in the hippocampus of patients with early or intermediate stage DLB. Hence, damage of neurons seems to be an early alteration in DLB.     

A new T677C mutation of the aspartoacylase gene encodes for a protein with no enzymatic activity

ObjectiveTo verify the effect of and to date the unknown T677C mutation of the human N-acetylaspartoacylase (hASPA) gene on the function of the mutated enzyme.Design and methodsWild type and I226T-mutated proteins were expressed and purified from a transformed Escherichia coli colony. Enzymatic activities were measured in the presence of varying substrate concentrations.ResultsWhilst kinetic parameters of wild type hASPA were in line with data in literature, I226T-mutated hASPA showed no enzymatic activity.ConclusionData indicated that this new mutation might be responsible in homozygosis for the phenotype corresponding to Canavan disease.     

Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study

Aims/hypothesis. It is increasingly evident that the brain is another site of diabetic end-organ damage. The pathogenesis has not been fully explained, but seems to involve an interplay between aberrant glucose metabolism and vascular changes. Vascular changes, such as deficits in cerebral blood flow, could compromise cerebral energy metabolism. We therefore examined cerebral metabolism in streptozotocin-diabetic rats in vivo by means of localised ³¹P and ¹H magnetic resonance spectroscopy. Methods. Rats were examined 2 weeks and 4 and 8 months after diabetes induction. A non-diabetic group was examined at baseline and after 8 months. Results. In ³¹P spectra the phosphocreatine:ATP, phosphocreatine:inorganic phosphate and ATP:inorganic phosphate ratios and intracellular pH in diabetic rats were similar to controls at all time points. In ¹H spectra a lactate resonance was detected as frequently in controls as in diabetic rats. Compared with baseline and 8-month controls ¹H spectra did, however, show a statistically significant decrease in N-acetylaspartate:total creatine (–14 % and –23 %) and N-acetylaspartate:choline (–21 % and –17 %) ratios after 2 weeks and 8 months of diabetes, respectively. Conclusion/interpretation. No statistically significant alterations in cerebral energy metabolism were observed after up to 8 months of streptozotocin-diabetes. These findings indicate that cerebral blood flow disturbances in diabetic rats do not compromise the energy status of the brain to a level detectable by magnetic resonance spectroscopy. Reductions in N-acetylaspartate levels in the brain of STZ-diabetic rats were shown by ¹H spectroscopy, which could present a marker for early metabolic or functional abnormalities in cerebral neurones in diabetes. [Diabetologia (2001) 44: 346–353] Received: 3 August 2000 and in revised form: 17 October 2000