N-acetylaspartate Levels Research Articles

Transient neonatal hyperglycemia induces metabolic shifts in the rat hippocampus: a 1H NMR-based metabolomics analysis.

Diabetes has been reported to induce brain metabolic disturbance, but the effect of transient neonatal hyperglycemia (TNH) on brain metabolism remains unclear. Herein the rats were treated with a single intraperitoneal injection of 100µg/g body weight of streptozotocin within 12h after birth and displayed a typical clinical characteristic of TNH. Then we used NMR-based metabolomics to examine the metabolic changes in the hippocampus between TNH and normal control (Ctrl) rats at postnatal 7 days (P7) and 21 days (P21). The results show that TNH rats had significantly increased levels of N-acetyl aspartate, glutamine, aspartate and choline in the hippocampus relative to Ctrl rats at P7. Moreover, we found that the levels of alanine, myo-inositol and choline were significantly lower in TNH rats, although their blood glucose levels have been recovered to the normal level at P21. Therefore, our results suggest that TNH may have a long-term effect on hippocampal metabolic changes mainly involving neurotransmitter metabolism and choline metabolism.

Adeno-associated virus-mediated gene therapy in a patient with Canavan disease using dual routes of administration and immune modulation

Gene replacement therapy is a rational therapeutic strategy and clinical intervention for neurodegenerative disorders like Canavan disease, a leukodystrophy caused by biallelic mutations in the aspartoacylase (ASPA) gene. We aimed toinvestigate whether simultaneous intravenous (i.v.) and intracerebroventricular (i.c.v.) administration of rAAV9-CB6-ASPA provides a safe and effective therapeutic strategy in an open-label, individual-patient, expanded-access trial for Canavan disease. Immunomodulation was given prophylactically prior to adeno-associated virus (AAV) treatment toprevent an immune response to ASPA or the vector capsid. The patient served as his own control, and change from baseline was assessed by clinical pathology tests, vector genomes in the blood, antibodies against ASPA and AAV capsids, levels of cerebrospinal fluid (CSF) N-acetylaspartate (NAA), brain water content and morphology, clinical status, and motor function tests. Two years post treatment, the patient's white matter myelination had increased, motor function was improved, and he remained free of typical severe epilepsy. NAA level was reduced at 3months and remained stable up to 4 years post treatment. Immunomodulation prior to AAV exposure enables repeat dosing and has prevented an anti-transgene immune response. Dual-route administration of gene therapy may improve treatment outcomes.

Microbleeds Due to Reperfusion Enhance Early Seizures after Carotid Ligation in a Rat Ischemic Model.

Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

A very rare cause of leukoencephalopathy: Lymphomatosis cerebri.

Leukoencephalopathy is a common finding on Magnetic Resonance Imaging (MRI), particularly in the elderly. A differential diagnosis may represent a very bet for clinicians when clear elements for diagnosis are lacking. Diffuse infiltrative "non mass like" leukoencephalopathy on MRI may represent the presentation of a very rare aggressive condition known as lymphomatosis cerebri (LC). The lack of orienting data, such as contrast enhancement on MRI or specific findings on examination of Cerebrospinal Fluid (CSF) or blood tests, may even far more complicate such a difficult diagnosis and orientate toward a less aggressive but time-losing mimic. A 69-old man initially presented to the Emergency Department (ED) complaining the recent appearance of unsteady walking, limitation of down and upgaze palsy, and hypophonia. Brain MRI revealed the presence of multiple, confluent hyperintense lesions on T2/Flair Attenuated Imaging Recovery (FLAIR) sequences involving either the withe matter of the semi-oval centres, juxtacortical structures, basal ganglia, or bilateral dentate nuclei. DWI sequences showed a wide restriction signal in the same brain regions but without any sign of contrast enhancement. Initial 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG PET) and CSF studies were not relevant. Brain MRI revealed a high choline-signal, abnormal Choline/ N-Acetyl-Aspartate (NAA), and Choline/Creatine (Cr) ratios, as well as reduced NAA levels. Finally, a brain biopsy revealed the presence of diffuse large B-cell lymphomatosis cerebri. The diagnosis of lymphomatosis cerebri remains elusive. The valorisation of brain imaging may induce clinicians to suspect such a difficult diagnosis and go through the diagnostic algorithm.

γ-Aminobutyric acid as a biomarker of the lateralizing and monitoring drug effect in patients with magnetic resonance imaging-negative temporal lobe epilepsy.

Despite verifying proton magnetic resonance spectroscopy (1H-MRS) for focal localization in magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE), it is necessary to illustrate metabolic changes and screen for effective biomarkers for monitoring therapeutic effect. We used 1H-MRS to investigate the role of metabolic levels in MRI-negative TLE. Thirty-seven patients (n = 37, 14 women) and 20 healthy controls (n = 20, 11 women) were investigated by 1H-MRS. We compared the metabolite level changes in the epileptic and contralateral sides on the mesial temporal and dorsolateral prefrontal cortices and analyzed their association with clinical symptoms. γ-Aminobutyric acid (GABA) levels were significantly lower on the epileptic side (2.292 ± 0.890) than in the contralateral side (2.662 ± 0.742, p = 0.029*) in patients on the mesial temporal lobe. N-acetylaspartate (NAA) levels were significantly lower on the epileptic side (7.284 ± 1.314) than on the contralateral side (7.655 ± 1.549, p = 0.034*). NAA + N-acetylaspartylglutamate levels were significantly lower on the epileptic side (7.668 ± 1.406) than on the contralateral side (8.086 ± 1.675, p = 0.032*). Glutamate levels were significantly lower on the epileptic side (7.773 ± 1.428) than on the contralateral side (8.245 ± 1.616, p = 0.040*). Moreover, a significant negative correlation was found between GABA levels in the epileptic mesial temporal lobe and tonic-clonic seizure frequency (r = -0.338, p = 0.046*). γ-Aminobutyric acid (GABA) is a potential biomarker for lateralization and monitoring seizure frequency in MRI-negative TLE.

BDNF rs6265 Met carriers with alcohol use disorder show greater age-related decline of N-acetylaspartate in left dorsolateral prefrontal cortex

BackgroundBrain-derived neurotrophic factor (BDNF) is implicated in neuronal and glial cell growth and differentiation, synaptic plasticity, and apoptotic mechanisms. A single-nucleotide polymorphism of the BDNF rs6265 gene may contribute to the pattern and magnitude of brain metabolite abnormalities apparent in those with an Alcohol Use Disorder (AUD). We predicted that methionine (Met) carriers would demonstrate lower magnetic resonance spectroscopy (MRS) measures of N-acetylaspartate level (NAA) and greater age-related decline in NAA than valine (Val) homozygotes. MethodsVeterans with AUD (n=95; 46±12 years of age, min = 25, max = 71) were recruited from VA Palo Alto residential treatment centers. Single voxel MRS, at 3 Tesla, was used to obtain NAA, choline (Cho) and creatine (Cr) containing compounds from the left dorsolateral prefrontal cortex (DLPFC). Metabolite spectra were fit with LC Model and NAA and Cho were standardized to total Cr level and NAA was also standardized to Cho. ResultsVal/Met (n=35) showed markedly greater age-related decline in left DLPFC NAA/Cr level than Val/Val (n=60); no differences in mean metabolite levels were observed between Val/Met and Val/Val. Val/Met demonstrated greater frequency of history of MDD and higher frequency of cannabis use disorder over 12 months prior to study. ConclusionsThe greater age-related decline in left DLPFC NAA/Cr and the higher frequency of MDD history and Cannabis Use disorder in BDNF rs6265 Met carriers with AUD are novel and may have implications for non-invasive brain stimulation targeting the left DLFPC and other psychosocial interventions typically utilized in the treatment of AUD.

Abnormal immune system response in the brain of women with Fibromyalgia after experimental endotoxin challenge

BackgroundThe pathophysiology of fibromyalgia (FM) is thought to include an overactive immune system, leading to central nervous system sensitization, allodynia, and hyperalgesia. We aimed to test this theory using an experimental immune system activation procedure and neuroimaging with magnetic resonance spectroscopic imaging (MRSI). MethodsTwelve women with FM and 13 healthy women (healthy controls; HC) received 0.3 or 0.4 ng/kg endotoxin and underwent MRSI before and after the infusion. Changes in brain levels of choline (CHO), myo-inositol (MI), N-Acetylaspartate (NAA), and MRSI-derived brain temperature were compared between groups and dosage levels using mixed analyses of variance. ResultsSignificant group-by-time interactions in brain temperature were found in the right thalamus. Post-hoc testing revealed that brain temperature increased by 0.55 °C in the right thalamus in FM (t(10) = -3.483, p = 0.006), but not in HCs (p > 0.05). Dose-by-time interactions revealed brain temperature increases in the right insula after 0.4 ng/kg (t(12) = -4.074, p = 0.002), but not after 0.3 ng/kg (p > 0.05). Dose-by-time interactions revealed decreased CHO in the right Rolandic operculum after 0.4 ng/kg endotoxin (t(13) = 3.242, p = 0.006) but not 0.3 ng/kg. In the left paracentral lobule, CHO decreased after 0.3 ng/kg (t(9) = 2.574, p = 0.030) but not 0.4 ng/kg. Dose-by-time interactions affected MI in several brain regions. MI increased after 0.3 ng/kg in the right Rolandic operculum (t(10) = -2.374, p = 0.039), left supplementary motor area (t(9) = -2.303, p = 0.047), and left occipital lobe (t(10) = -3.757, p = 0.004), with no changes after 0.4 ng/kg (p > 0.05). Group-by time interactions revealed decreased NAA in the left Rolandic operculum in FM (t(13) = 2.664, p = 0.019), but not in HCs (p > 0.05). A dose-by-time interaction showed decreased NAA in the left paracentral lobule after 0.3 ng/kg (t(9) = 3.071, p = 0.013) but not after 0.4 ng/kg (p > 0.05). In the combined sample, there was a main effect of time whereby NAA decreased in the left anterior cingulate (F[1,21] = 4.458, p = 0.047) and right parietal lobe (F[1,21] = 5.457, p = 0.029). ConclusionWe found temperature increases and NAA decreases in FM that were not seen in HCs, suggesting that FM patients may have abnormal immune responses in the brain. The 0.3 and 0.4 ng/kg had differential effects on brain temperature and metabolites, with neither dose effecting a stronger response overall. There is insufficient evidence provided by the study to determine whether FM involves abnormal central responses to low-level immune challenges.

Associations between N-Acetylaspartate and white matter integrity in individuals with schizophrenia and unaffected relatives.

Compromised white matter has been reported in schizophrenia; however, few studies have investigated neurochemical abnormalities underlying microstructural differences. N-acetylaspartate (NAA) is used to synthesize myelin and is often reduced in persons with schizophrenia (PSZ) and their unaffected first-degree relatives (REL). Low levels of NAA could affect white matter by preventing the synthesis or repair of myelin. We used magnetic resonance spectroscopy and diffusion tensor imaging to investigate the relationship between NAA and white matter integrity in PSZ. REL were included to examine whether putative relationships are associated with symptom expression or illness liability. 52 controls, 23 REL and 25 PSZ underwent 7T proton magnetic resonance spectroscopy and/or 3T diffusion tensor imaging. NAA in the visual cortex and basal ganglia were measured and compared across groups. Diffusivity measures were compared across groups using tract-based spatial statistics and related to NAA concentrations. Visual cortex NAA was significantly reduced in PSZ compared to controls. White matter integrity did not differ between groups. Reduced cortical and subcortical NAA were associated with diffusivity measures of poor white matter microstructure. These data suggest that levels of neural NAA may be related to white matter integrity similarly across individuals with schizophrenia, those at genetic risk, and controls.

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology

Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology

Could thalamic biochemical changes correlate to cognitive impairment in idiopathic generalized epilepsy?

BackgroundThe thalamus is crucial in the development of idiopathic generalized epilepsy (IGE), which could lead to cognitive dysfunctions, according to data from neuropsychology and advanced neuroimaging investigations. This research aimed to measure the metabolic changes in the thalamus and to assess if could be contributed to cognitive impairment in IGE patients. Thirty IGE patients and thirty healthy volunteers with matched ages, genders, and educational levels participated in this cross-sectional case–control research. The IGE patients and controls were evaluated neuropsychologically using Intelligence Quotient (IQ) to assess general cognitive ability, Digit span for attention, Wechsler memory scale (WMS) for verbal memory, cube drawing test for visuospatial memory, Trail making test for executive functions, and Controlled Oral Word Association test (COWAT) for verbal fluency and quantitative multi-voxel MR spectroscopy (MRS) measurements of N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, NAA/Cho and Cho/Cr ratios at 1.5 T scanner. The voxels were located over the right and left thalamus.ResultsThe IGE patients showed worse cognitive performance in IQ, attention, executive function, and verbal and visuospatial memory domains compared to the controls. The IGE patients exhibited a significantly decrease NAA in the right thalamus (p = 0.004) and a lower NAA/Cr ratio in the left thalamus (p = 0.01). the mean thalamus NAA level exhibited a positive correlation with CDT (r = 0.45, p = P = 0.01), and WMS-R (r = 0.39, p = 0.03) and a negative correlation with trail-making A test (r = 0.42, P = 0.01).Conclusionsit was concluded that IGE patients exhibited poor cognition which could be attributed to thalamic neurometabolic changes due to impaired thalamic cortical circuits.

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa.

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Whole-brain MR spectroscopic imaging reveals regional metabolite abnormalities in perinatally HIV infected young adults.

Perinatally acquired HIV (PHIV) has been associated with brain structural and functional deficiencies, and with poorer cognitive performance despite the advent of antiretroviral therapy (ART). However, investigation of brain metabolite levels in PHIV measured by proton magnetic resonance spectroscopy (MRS) methods, is still limited with often inconclusive or contradictory findings. In general, these MRS-based methods have used a single voxel approach that can only evaluate metabolite concentrations in a few select brain anatomical regions. Additionally, most of the published data have been on children perinatally infected with HIV with only a few studies examining adult populations, though not exclusively. Therefore, this prospective and cross-sectional study aims to evaluate metabolite differences at the whole-brain level, using a unique whole-brain proton magnetic resonance spectroscopy imaging (MRSI) method, in a group of PHIV infected young adults (N = 28) compared to age and gender matched control sample (N = 28), and to find associations with HIV clinical factors and neurocognitive scores. MRSI data were acquired on a 3T scanner with a TE of 70 ms. Brain metabolites levels of total N-acetylaspartate (tNAA), total choline (tCho) and total creatine (tCre), as well as ratios of tNAA/tCre, tCho/tCre, and tNAA/tCho, were obtained from the whole brain level and evaluated at the level of gray matter (GM) and white matter (WM) tissue types and anatomical regions of interest (ROI). Our results indicate extensive metabolic abnormalities throughout the brains of PHIV infected subjects with significantly elevated levels of tCre and tCho, notably in GM regions. Decreases in tNAA and ratios of tNAA/tCre and tNAA/tCho were also found mostly in WM regions. These metabolic alterations indicate increased glial activation, inflammation, neuronal dysfunction, and energy metabolism in PHIV infected individuals, which correlated with a reduction in CD4 cell count, and lower cognitive scores. Our findings suggest that significant brain metabolite alterations and associated neurological complications persist in the brains of those with PHIV on long-term ART, and advocates the need for continued monitoring of their brain health.

Neurometabolite alterations in traumatic brain injury and associations with chronic pain.

Traumatic brain injury (TBI) can lead to a variety of comorbidities, including chronic pain. Although brain tissue metabolite alterations have been extensively examined in several chronic pain populations, it has received less attention in people with TBI. Thus, the primary aim of this study was to compare brain tissue metabolite levels in people with TBI and chronic pain (n = 16), TBI without chronic pain (n = 17), and pain-free healthy controls (n = 31). The metabolite data were obtained from participants using whole-brain proton magnetic resonance spectroscopic imaging (1H-MRSI) at 3 Tesla. The metabolite data included N-acetylaspartate, myo-inositol, total choline, glutamate plus glutamine, and total creatine. Associations between N-acetylaspartate levels and pain severity, neuropathic pain symptom severity, and psychological variables, including anxiety, depression, post-traumatic stress disorder (PTSD), and post-concussive symptoms, were also explored. Our results demonstrate N-acetylaspartate, myo-inositol, total choline, and total creatine alterations in pain-related brain regions such as the frontal region, cingulum, postcentral gyrus, and thalamus in individuals with TBI with and without chronic pain. Additionally, NAA levels in the left and right frontal lobe regions were positively correlated with post-concussive symptoms; and NAA levels within the left frontal region were also positively correlated with neuropathic pain symptom severity, depression, and PTSD symptoms in the TBI with chronic pain group. These results suggest that neuronal integrity or density in the prefrontal cortex, a critical region for nociception and pain modulation, is associated with the severity of neuropathic pain symptoms and psychological comorbidities following TBI. Our data suggest that a combination of neuronal loss or dysfunction and maladaptive neuroplasticity may contribute to the development of persistent pain following TBI, although no causal relationship can be determined based on these data.

An enzymatic fluorimetric assay for determination of N-acetylaspartate

N-acetylaspartate (NAA) is an abundant metabolite in the mammalian brain and a precursor of the neuropeptide N-acetylaspartylglutamate (NAAG). The physiological role of NAA is not fully understood and requires further studies. We here describe the development of a coupled enzymatic fluorimetric assay for the determination of NAA in biological samples. Deproteinized tissue extracts are first passed through a strong cation exchange column to remove aspartate. NAA in the sample is hydrolysed by aspartoacylase and released aspartate oxidized using l-aspartate oxidase. Generated H2O2 is measured with peroxidase in a fluorimetric assay using Ampliflu Red. The limit of detection and the lower limit of quantification are 1.0 μM (10 pmol/well) and 3.3 μM (33 pmol/well), respectively, with a linear range to 100 μM. Specificity of the assay was confirmed using samples from mice deficient in NAA synthase Nat8l that were spiked with NAA. Analysis of samples from aspartoacylase-deficient mice showed a 2 to 3-fold increase in brain NAA concentration, in line with previous reports. Mice lacking NAAG synthetases had a slightly reduced (−10%) brain NAA level. Thus, the new fluorimetric enzymatic assay is useful to perform sensitive and large scale quantification of NAA in biological samples without the need for expensive equipment.

Correlation between abnormal N-acetyl-aspartate levels in posterior cingulate cortex and persistent auditory verbal hallucinations in Chinese patients with chronic schizophrenia

The aim of this study was to investigate the relationship between persistent auditory verbal hallucinations (pAVHs) and N-acetyl-aspartate (NAA) levels in posterior cingulate cortex (PCC). 117 schizophrenia (SCZ) patients (61 pAVHs and 56 non-AVHs) and 66 healthy controls were included. The P3 item of the Positive and Negative Syndrome Scale and the Auditory Hallucinations subscale of the Psychotic Symptom Rating Scale were used to assess the severity of pAVHs. NAA levels were significantly lower in the AVHs group, and were negatively correlated with pAVHs. Therefore, increasing the NAA levels in PCC may be helpful in treating pAVHs.

Association between brain N-acetylaspartate levels and sensory and motor dysfunction in patients who have spinal cord injury with spasticity: an observational case-control study.

Spinal cord injury is a severe and devastating disease, and spasticity is a common and severe complication that is notoriously refractory to treatment. However, the pathophysiological mechanisms underlying spasticity and its development remain largely unknown. The goal of the present study was to find differences, if any, in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity, and to explore the relationship between the brain metabolite concentrations and clinical status. Thirty-six participants were recruited for magnetic resonance spectroscopic examination: 23 with spinal cord injury (12 with spasticity and 11 without spasticity) and 13 healthy controls. We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm3 voxels. Notably, univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration (a marker for neuronal loss) was in the precentral gyrus of the patients, the lower their ASIA (American Spinal Injury Association) light-touch scores, pinprick scores, and motor scores. Additionally, longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus. Compared with the healthy participants and patients without spasticity, N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia. Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

Normal Appearing White Matter N-Acetylaspartate Changes Impact on Fatigue in Multiple Sclerosis

Background: Fatigue is one of the most frequent complaints presented by multiple sclerosis patients. Fatigue may be multifactorial. Proton magnetic resonance spectroscopy studies have shown significant reductions in N-acetylaspartate/creatine ratios in multiple brain regions among fatigued multiple sclerosis patients in comparison to non-fatigued multiple sclerosis patients, suggesting axonal loss as a contributing factor. Females are twice as likely to develop the disease. Aim: To evaluate gender variability in fatigue scores in relapsing-remitting multiple sclerosis patients. To explore potential gender differences in metabolite profiles of normal appearing white matter. To correlate metabolite changes distribution with fatigue severity and to evaluate the gender impact. Methods: We enrolled 50 relapsing-remitting multiple sclerosis patients on disease modifying treatment and 28 healthy controls. All participants underwent proton magnetic resonance spectroscopy of normal appearing white matter corresponding regions and fatigue severity evaluation. Results: We found higher fatigue scores in the multiple sclerosis group, due to greater severity in female subjects. We found a significant decrease of N-acetylaspartate/creatine ratio with increase in N-acetylaspartate, choline, and creatine levels in multiple sclerosis subjects. N-acetylaspartate and choline levels were significantly higher in the multiple sclerosis males. Female multiple sclerosis patients presented with lower N-acetylaspartate levels than healthy controls and greater increases in Fatigue Severity Scale score. Regression analysis revealed metabolite specific relationships between fatigue against metabolite variables. Conclusion: Proton magnetic resonance spectroscopy registered differences in metabolite profiles in normal appearing white matter male and female multiple sclerosis subjects. We might presume gender dependent specifiers in metabolite profiles in relapsing- remitting multiple sclerosis. They impact fatigue severity. N- acetyaspartate might be crucial contributor in central fatigue in multiple sclerosis. Bioenergetic role of N-acetylaspartate needs further collaborative research on genetics and electrical properties of neurons to reveal the underlying mechanism of fatigue and conductivity deterioration.

Levels of N-acetylaspartate are associated with cortical thickness in Covid-19 survivors

Levels of N-acetylaspartate are associated with cortical thickness in Covid-19 survivors

Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming.

Various comorbid psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD), have been reported in individuals with internet gaming disorder (IGD). Prior research has shown alterations in brain metabolites, including N-acetylaspartate (NAA), and combined glutamate and glutamine in patients with ADHD that were similar to those observed in patients with IGD. We hypothesized that the decreased NAA levels in the IGD group would be associated with a history of ADHD. Forty adults participated in this study. Participants were classified as having a high risk for IGD if they had a total score higher than 21 on the IGD Scale-short form. Proton magnetic resonance spectroscopy (1H-MRS) and high-resolution structural magnetic resonance imaging (MRI) data were acquired using a 3 Tesla Siemens Prisma scanner system. Levels of NAA within the right prefrontal cortex were lower in the IGD group than those observed in the control group. In a multiple linear regression analysis, internet addiction test scores and history of ADHD were shown to predict increased game play. In addition, history of ADHD predicted lower levels of NAA within the right prefrontal cortex. The preliminary results of current study suggest a mediating effect of ADHD on the severity of internet game play as well as the levels of NAA within the dorsolateral prefrontal cortex (DLPFC). The inclusion of ADHD in IGD research is important and deserving of further consideration.

Hippocampal Neuronal Integrity and Functional Connectivity Within the Default Mode Network in Mild Cognitive Impairment: A Multimodal Investigation.

Background: In older people with mild cognitive impairment (MCI), the relationship between early changes in functional connectivity and in vivo changes in key neurometabolites is not known. Two established correlates of MCI diagnosis are decreased N-acetylaspartate (NAA) in the hippocampus, indicative of decreased neuronal integrity, and changes in the default mode network (DMN) functional network. If and how these measures interrelate is yet to be established, and such understanding may provide insight into the processes underpinning observed cognitive decline. Objectives: To determine the relationship between NAA levels in the left hippocampus and functional connectivity within the DMN in an aging cohort. Methods: In a sample of 51 participants with MCI and 30 controls, hippocampal NAA was determined using magnetic resonance spectroscopy, and DMN connectivity was quantified using resting-state functional MRI. The association between hippocampal NAA and the DMN functional connectivity was tested within the MCI group and separately within the control group. Results: In the DMN, we showed a significant inverse association between functional connectivity and hippocampal NAA in 20 specific brain connections for patients with MCI. This was despite no evidence of any associations in the healthy control group or group differences in either of these measures alone. Conclusions: This study suggests that decreased neuronal integrity in the hippocampus is associated with functional change within the DMN for those with MCI, in contrast to healthy older adults. These results highlight the potential of multimodal investigations to better understand the processes associated with cognitive decline. Impact statement This study measured activity within the default mode network (DMN) and quantified N-acetylaspartate (NAA), a measure of neuronal integrity, within the hippocampus in participants with mild cognitive impairment (MCI) and healthy controls. In participants with MCI, NAA levels were inversely associated with connectivity between specific regions of the DMN, a relationship not evident in healthy controls. This association was present even in the absence of group differences in DMN connectivity or NAA levels. This research illustrates the possibility of using multiple magnetic resonance modalities for more sensitive measures of early cognitive decline to identify and intervene earlier.