Metabolites In Hippocampus Research Articles

Testosterone's anti-anxiety and analgesic effects may be due in part to actions of its 5α-reduced metabolites in the hippocampus

Although testosterone (T) may have effects to enhance analgesia and reduce anxiety, its effects and mechanisms are not well understood. We hypothesized that if T's anti-anxiety and analgesic effects are due in part to actions of its 5alpha-reduced metabolite (dihydrotestosterone-DHT) and/or its 3alpha-hydroxysteroid dehydrogenase reduced metabolite (3alpha-androstanediol-3alpha-diol), in the hippocampus, then androgen regimens that increase levels of these metabolites in the hippocampus should produce anti-anxiety behavior, and analgesic effects, in gonadectomized (GDX) male rats. In Experiment 1, GDX rats were administered T, DHT, 3alpha-diol (1 mg/kg, SC), or vehicle. In Experiment 2, GDX rats had T, DHT, 3alpha-diol-containing inserts, or empty control inserts applied to the dorsal hippocampus immediately prior to behavioral testing. Androgen-administered rats (SC or intrahippocampal) showed significantly more exploratory behavior in the open field and elevated plus maze, less freezing in response to shock, and longer tailflick and pawlick latencies. These findings suggest that T's anti-anxiety effects may be due in part to actions of its 5alpha-reduced metabolites in the dorsal hippocampus.

Long-term follow-up of magnetic resonance-detectable choline signal changes in the hippocampus of patients treated with electroconvulsive therapy.

In a previous proton magnetic resonance spectroscopic imaging ((1)H MRSI) study of the hippocampus in patients receiving electroconvulsive therapy (ECT), the metabolite signals for N-acetylaspartate (NAA), creatine and phosphocreatine, and choline-containing compounds (Ch) were evaluated before and directly after a course of ECT. Stable metabolite signals for NAA and creatine and phosphocreatine but increasing signals from choline-containing compounds post-ECT compared with pre-ECT were found. The purpose of this investigation was to monitor the long-term course of the hippocampal metabolite signals post-ECT treatment. Twelve of 17 depressed patients (DSM-IV and ICD-10 criteria), examined while receiving ECT, were reevaluated after a minimum interval of 12 months. Data were gathered between 1997 and 2000. In all patients, (1)H MRSI studies of the hippocampus were performed and relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined. Patients' cognitive as well as psychopathologic status was obtained. Two of the examined patients suffered a relapse. All other patients were in stable remission. No changes in hippocampal NAA signals were detected after a mean interval of 20 months (SD = 8.6) after the last ECT. The initially significant increase in the Ch signal was found to be reversed to nearly pre-ECT values. The results of our long-term follow-up corroborate our original finding that ECT has no influence on NAA signals. The observed reversal of the Ch signal might reflect alterations in membrane turnover. Increased Ch signals are thought to reflect an increased membrane turnover and should reverse accordingly. This increase in membrane turnover could potentially play a role in the therapeutic effect of ECT.

A Fully Automated Method for Tissue Segmentation and CSF-Correction of Proton MRSI Metabolites Corroborates Abnormal Hippocampal NAA in Schizophrenia

In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients.

Reproducibility of hippocampal single-Voxel proton MR spectroscopy and chemical shift imaging.

We investigated between- and within-acquisition reproducibility of hippocampal metabolite ratios obtained using automated proton MR spectroscopy. We examined 30 healthy adults with a 1.5-T scanner four times on 3 days using single-voxel spectroscopy over the left hippocampus, chemical shift imaging over the left hippocampus, and chemical shift imaging over the bilateral hippocampi. Metabolite ratios were derived from the integral values of three major peaks: N:-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr). The random-effects model of one-way analysis of variance was used to evaluate the reproducibility in terms of coefficient of variation; the mixed-effects model was used to compare the results of different hippocampal regions and spectroscopic techniques. Most coefficients of variation for the NAA/(Cho+Cr) ratio were less than 20%. All the coefficients of variation for the posterior hippocampus (15-25%) were less than those for the anterior hippocampus (20-44%). The posterior hippocampal NAA/(Cho+Cr) ratio of unilateral chemical shift imaging had the lowest coefficient of variation (<16%). Single-voxel spectroscopy and unilateral chemical shift imaging had similar coefficients of variation for the anterior hippocampal NAA/(Cho+Cr) ratios (17-20%). There was a significant difference in metabolite ratios measured in different hippocampal regions (p<0.01) and in those acquired with different spectroscopic techniques (p<0.001). The NAA/(Cho+Cr) ratio is the most reproducible parameter for hippocampal MR spectroscopy on a 1.5-T scanner. Regional variation and technical differences in metabolite ratios must be considered when interpreting proton spectra of the hippocampus.

Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic resonance spectroscopy and imaging study of the hippocampus/amygdala complex.

We have used proton magnetic resonance imaging and spectroscopy to measure hippocampus/amygdala volumes and anterior hippocampal metabolite concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline) in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal controls. Four groups of right-handed patients were selected: 12 with TLE and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia, and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa GE scanner. The schizophrenia group showed a significant left-sided reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally. The NAA reduction in the EP group was greater than in the ENP group, especially on the left, although the result did not reach significance. Total hippocampus/amygdala volumes showed no significant differences in any of the groups when compared with normal controls. When compared with controls significant, specific regional volume reductions were present bilaterally in the EP group and in the left hippocampus/amygdala in schizophrenia. The regional volume reduction found in schizophrenia was also present in EP but not in ENP. Spectroscopic abnormalities were more pronounced in the epilepsy groups and were bilateral, and abnormalities in schizophrenia were left sided. Specific regional hippocampus/amygdala volume reductions were more marked in the EP group and were bilateral. Left-sided regional volume reduction identified in the dominant hemisphere of schizophrenics was also present in EP patients, but not in ENP, suggesting that this region in the left temporal lobe may be significant in the aetiology of psychosis. This is further supported by the predominantly left-sided NAA reduction in schizophrenia. High resolution morphometric studies may identify specific regions of the brain associated with the development of psychosis.

Cognitive correlates of 1H MRSI-detected hippocampal abnormalities in temporal lobe epilepsy.

To examine associations between 1H magnetic resonance spectroscopic imaging (1H MRSI)-detected hippocampal creatine to N-acetylaspartate (Cr/NAA) ratios and neuropsychological measures sensitive to mesial temporal lobe function. The measurement of 1H MRSI-detected hippocampal metabolites has proved effective in determining extent and lateralization of neuronal damage. However, relationships between 1H MRSI-detected hippocampal metabolic abnormalities and specific areas of cognitive functioning have received limited attention compared to other studies using MRI volumetry or cerebral blood flow techniques. We analyzed right and left hippocampal Cr/NAA ratios in 46 adult mesial temporal lobe epilepsy patients (32 left, 14 right) by 1H MRSI at high magnetic field (4.1 T). We examined the relationship between the right and left Cr/NAA hippocampal ratios to measures of verbal and visual memory, intelligence, attention, visuoperception, and confrontation naming. Measures of episodic verbal memory (n = 33) and visual confrontation naming (n = 46) were selectively associated with left hippocampal metabolic function (p<0.004), whereas neuronal function of the right hippocampal region was strongly associated with performance on a measure of facial recognition (n = 46; p<0.02). This study shows that specific areas of cognitive function are related to hippocampal neuronal metabolic abnormalities as detected by spectroscopic imaging. The current study indicates that 1H MRSI offers a complimentary technique to structural imaging studies in the study of mesial temporal lobe epilepsy and may enhance understanding of the role of hippocampal function in complex cognitive systems.

Age-related metabolite changes and volume loss in the hippocampus by magnetic resonance spectroscopy and imaging☆

Magnetic resonance imaging (MRI) studies have produced controversial results concerning the correlation of hippocampal volume loss with increasing age. The goals in this study were: 1) to test whether levels of N-acetyl aspartate (NAA, a neuron marker) change in the hippocampus during normal aging and 2) to determine the relationship between hippocampal NAA and volume changes. Proton magnetic resonance spectroscopic imaging (1H MRSI) and MRI were used to measure hippocampal metabolites and volumes in 24 healthy adults from 36 to 85 years of age. NAA/Cho decreased by 24% (r = 0.53, p = 0.01) and NAA/Cr by 26% (r = 0.61, p < 0.005) over the age range studied, whereas Cho/Cr remained stable, implying diminished NAA levels. Hippocampal volume shrank by 20% (r = 0.64, p < 0.05). In summary, aging effects must be considered in 1H MRSI brain studies. Furthermore, because NAA is considered a marker of neurons, these results provide stronger support for neuron loss in the aging hippocampus than volume measurements by MRI alone.

Quantitative 1H MRS in the evaluation of mesial temporal lobe epilepsy in vivo

Hippocampal metabolite concentrations were determined by localized in vivo proton magnetic resonance spectroscopy ( 1H MRS) in eleven patients suffering from refractory mesial temporal lobe epilepsy (MTLE), as well as in eleven age-matched healthy volunteers, and compared with patient history, postoperative outcome and histopathology. Main results are: 1) In patients, the decrease in N-acetylaspartate (NAA) concentrations was highly significant ipsilateral, and less but still significant contralateral to the electroencephalogram-defined focus, as compared to controls. 2) The decrease in ipsilateral NAA measured preoperatively correlates with the degree of hippocampal sclerosis but 3) does not reliably predict postoperative outcome, although there is a trend toward better outcome in patients with a marked decrease of NAA. 4) Hippocampal NAA decrease (ipsi- and contralateral) is highly correlated with early onset age of epileptic seizures. 5) Among patients with similar onset age in early childhood, there is a strong association between duration of the disease and contralateral (and, though less clear-cut, ipsilateral) NAA loss. These results are concordant with the notion of a generally progressive worsening and complicating course of symptoms in poorly controlled MTLE.

Increase in dopamine turnover and tyrosine hydroxylase enzyme in hippocampus of rats fed on low selenium diet.

We have studied the turnover of dopamine, noradrenaline, and serotonin and their metabolites in hippocampus of adult female rats that were fed control or selenium-deficient diets during 15 days. Under these circumstances, there was an increase of dopamine turnover (4-fold) in rats fed with selenium-deficient diet with respect to controls and also an increase in the tyrosine hydroxylase activity (75.8%), which was the result of the increase of the amount of the enzyme (2-fold), without significant change in the phosphorylation of the tyrosine hydroxylase. In addition the glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase activities have been studied. After selenium-deficient diet, the enzymatic activities of superoxide dismutase and catalase did not show change with respect to the controls; however glutathione reductase and glutathione peroxidase significantly decreased 15% and 29%, respectively. It is concluded that the increase in dopamine turnover seems to be associated with the induction of tyrosine hydroxylase enzyme. In these conditions the decrease in antioxidant capacity may produce a cascade of events, which accelerates the degenerative process, since the increase in dopamine turnover produces an increase in oxygen radical by monoamine oxidase activity.