A functional model for the aspartate/glutamate carrier of the inner mitochondrial membrane was established based on a kinetic evaluation of this transporter. Antiport kinetics were measured in proteoliposomes that contained partially purified carrier protein of definite transmembrane orientation (Dierks, T. and Krämer, R. (1988) Biochim. Biophys. Acta 937, 122-126). Bireactant initial velocity analyses of the counterexchange reaction were carried out varying substrate concentrations both in the internal and the external compartment. The kinetic patterns obtained were inconsistent with a pong-pong mechanism; rather they demonstrated the formation of a ternary complex as a consequence of sequential binding of one internal and one external substrate molecule to the carrier. Studies on transport activity in the presence of aspartate and glutamate in the same compartment (formally treated as substrate inhibition) clearly indicated that during exchange only one form of the carrier at either membrane surface exposes its binding sites, for which the two different substrates compete. In the deenergized state (pH 6.5) both substrates were translocated at about the same rate. Aspartate/glutamate antiport became asymmetric if a membrane potential was imposed, due to the electrogenic nature of the heteroexchange resulting from proton cotransport together with glutamate. Investigation of the electrical properties of aspartate/aspartate homoexchange led to the conclusion that the translocating carrier-substrate intermediate exhibits a transmembrane symmetry with respect to the (negative) charge, which again only is conceivable assuming a ternary complex. Thus, an antiport model is outlined that shows the functional complex of the carrier with two substrate molecules bound, one at either side of the membrane. The conformational change associated with the transition of both substrate molecules across the membrane then occurs in a single step. Furthermore the model implicates a distinct proton binding site, which is derived from the different influence of H+ concentration observed on transport affinity and transport velocity, respectively, when glutamate is used as a substrate.

Adenosine Diphosphate↗

PubMed1988

Asymmetric orientation of the reconstituted aspartate/glutamate carrier from mitochondria.

A partially purified preparation of the aspartate/glutamate carrier from bovine heart mitochondria was reconstituted into liposomal membranes by chromatography on hydrophobic ion exchange resins. Based on the favorable conditions of this reconstituted system the transmembrane orientation of the inserted carrier protein could be determined by functional analysis. For reliable measurement of the reconstituted aspartate-glutamate exchange activity an optimized inhibitor-stop technique using pyridoxal phosphate was developed. By simultaneous application of both forward and backward exchange experiments the practical usefulness of the reconstituted system could be extended to investigations including variation of internal and external substrate concentrations over a wide range. Thereby a complete set of Km values for both aspartate and glutamate at both the internal and external side of the proteoliposomes could be established. These experiments led to the following results and conclusions: (i) The observed substrate affinities are clearly different for the two different membrane sides both for aspartate (external 50 microM, internal 3 mM) and glutamate (external about 200 microM, internal 3 mM). (ii) The exclusive presence of only one type of transport affinity for every single substrate at one side of the liposomal membrane clearly demonstrates the asymmetric orientation of the functionally active carrier protein molecules. (iii) When comparing the values of these constants with published data obtained in mitochondria, an inside-out orientation of the aspartate/glutamate carrier after isolation and reinsertion into liposomes is strongly suggested.

Amino Acid Transport Systems, Acidic↗

PubMed1988

Topographic mapping of EEG and auditory evoked P300 in neuropsychopharmacology (topographic pharmaco-EEG and pharmaco-AEP 300).

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Adult↗

PubMed1988

Effects of pyritinol on the distribution of electrical brain activity.

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Alzheimer Disease↗

PubMed1988

[Topography of P300 in psychiatry--1. Cognitive P300 fields in psychoses].

P300 is known as a wave which enables the evaluation of cognitive function in neuropsychology and psychiatry. The most reliable result in psychoses was an amplitude reduction. Since similar wave alteration occurred not only in psychoses but also in dementia, the P300 reduction was too unspecific to serve as criteria for differential diagnosis. By means of topographical procedures it could be found out that the well defined P300 fields underwent characteristic changes in psychoses which even allowed a differentiation between different subgroups in schizophrenia. In hebephrenics the frontal field was very low whereas the paranoid group showed a lateralized P300-pattern with lower amplitudes in the right parieto-temporal area. In depression the P300-pattern was identical to the fields known in geriatric controls. The results will be discussed regarding other structural and functional imaging procedures. By means of topographical display of P300 the specificity of cognitive waves can be augmented considerably with the possibility to differentiate between different types of psychoses.

Affective Disorders, Psychotic↗

PubMed1988

[Topography of P300 in psychiatry--II. Cognitive P300 fields in dementia].

The P300 wave undergoes alterations during physiological aging showing lower amplitudes and longer latencies in geriatric controls. By means of topographical display of P300-data it could be shown that the topography with maximal positivity at parietal sites is maintained in aging. In patients, however, suffering from senile dementia of Alzheimer's type signs of a frontal elevation and a parietal decrement of P300 amplitudes could be observed. The findings can be interpreted firstly as an indication that the frontal lobe is less effected. On the other side if a hippocampal dipole is assumed a neuronal lesion could lead to a turn of this dipole with the result of a now frontally located positivity.

Adult↗

PubMed1988

[The topography of P300 in neuropsychiatric pharmacotherapy. III. Cognitive P300 fields in an organic psychosyndrome (Wilson's disease) before and during treatment with D-penicillamine].

Beside senile dementia of Alzheimer's type (SDAT) there are also dementive syndromes due to a disturbance in metabolism. In a case with a disturbance of copper metabolism (Wilson's disease) a similar P300-pattern was found as described in SDAT with signs of a frontal amplitude elevation. Under therapy with d-penicillamine the frontal P300-positivity moved from frontal to parietal structures. Combined with this migration was an amelioration in cognitive function. This single-case study underlines the significance of P300-topography in the evaluation of therapy effects in dementive disorders.

Adult↗

PubMed1987

Functional imaging of the brain in psychiatry--mapping of EEG and evoked potentials.

Topographic brain mapping of EEG and evoked potentials permits the display of spontaneous and event-related activity of the brain. This new method is superior to conventional polygraphy because of the topographic approach which delineates structural and functional brain lesions. Data from 16 to 20 scalp electrodes were evaluated. Not only spontaneous EEG but also EEG during various testing conditions which activated particular brain regions was measured. For EEG fast Fourier transformation (FFT) was used for mapping. For late evoked potentials (VEP, AEP, SEP and P300) a single value representing the amplitude of EP at each 2-ms poststimulus latency point was used. Statistical techniques (Students'-test, correlation coefficient) were used to render the regions where a clinical population differs from normal subjects. The results show abnormalities of EGG and EP in patients with psychiatric and neurological diseases.

Arousal↗

PubMed1987

[Brain mapping--topographic demonstration of the EEG and evoked potentials in psychiatry and neurology].

Brain mapping of EEG and evoked potentials permits the topographic display of electrical activity of the brain and is superior to conventional polygraphic procedures. Data from 16 scalp electrodes and two ear reference electrodes were worked up. The spontaneous EEG and the EEG during different testing conditions to activate particular brain regions was measured. 2 s EEG data segments were subjected to spectral analysis by a fast Fourier transformation (FFT). For late evoked potentials (VEP, AEP, SEP and P300) a single value representing the amplitude of EP at each 2-ms poststimulus latency point served for subsequent topographic mapping. Statistical techniques (Student's t-test) have been used in conjunction with EEG and EP data to render visible the regions where a clinical population differ from normal subjects. The results show abnormalities of EEG and EP in patients with psychical und neurological diseases.

Arousal↗

PubMedDate not supplied

Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type.

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

Aged↗