[Platelet cytochrome c-oxidase and glutamine synthetase-like protein in patients with mild cognitive impairment].

The study aimed to develop pre-clinical diagnosis of Alzheimer's disease (AD) and - in future - preventive therapy in patients with mild cognitive impairment (MCI). The MCI group (n=44) and AD group (n=42, including 18 patients with soft dementia and 24 patients with mild dementia) were studied. The groups were matched for age (median 70 and 69 years for MCI and AD groups, respectively). The control group comprised 24 mentally healthy relatives of the patients. Correlations between the activity/amounts of platelet enzymes: cytochrome c-oxidase (COX), glutamine synthetase-like protein (GSLP) and the extent of cognitive impairment were studied. The COX activity in MCI and AD groups was significantly lower than in the control group (Kruskal-Wallis test p=0.0001, χ²=11.6, p=0.003). These tests showed significant differences in GSLP amount between three groups (p=0.04 and χ²=9.38, p=0.01, respectively). Significant reverse correlation (Spearman R= -0.43, p=0.007) was found between GSLP amount and MMSE scores for MCI+AD group, i.e., the lower MMSE scores, the higher platelet GSLP level. Platelet COX and GSLP may be considered as early markers of cognitive impairment.

[Glutamine synthetase-like protein, glutamate dehydrogenase, and cytochrome c-oxidase in platelets of patients with the first episode psychosis in the course of treatment].

The authors searched for correlations between amounts of platelet proteins and results of psychometric tests in patients with the first episode psychosis (schizophrenia, schizoaffective psychosis) in the course of their combined antipsychotic treatment with haloperidol and clozapine. Psychometric evaluations (PANSS, BPRS) and analyses of platelet enzymes - glutamine synthetase-like protein (GSLP), glutamate dehydrogenase (GDH), and cytochrome c-oxidase (COX) - were carried out before, during, and after the treatment. These proteins were also analyzed in matched controls. All the parameters comprised a database, followed by statistical data processing using Statistica 6.0 (StatSoft) software, nonparametric statistics module. The patients before the treatment, when compared with controls, demonstrated significantly decreased COX activity (p=0,0000001) and increased GSLP amount (p=0,006) with a positive correlation between GSLP amount and PANSSneg (R=0,34, p<0,01). Those patients who displayed initially low COX activity (below median) demonstrated significant increase in COX activity after the treatment. Negative correlations were revealed between COX activity and PANSS, PANSSpsy scores during the treatment, i.e. the lower was COX activity, the more severe syndromes were observed. Negative correlations were found between the initial COX activity and PANSS, PANSSpsy, BPRS scores after the treatment, i.e., the higher was COX before the treatment, the less prominent syndromes were observed after the treatment. Significantly more "non-responders" by PANSSneg were found among the patients with low GSLP level (below median) than their calculated expected amount. The COX activity measured before the treatment was significantly lower in patients with schizophrenia than in patients with schizoaffective disorder (SAD) (p=0,038). In SAD patients, the initial COX activity was negatively correlated with PANSSpsy and BPRS scores after the treatment (R=-0,5, p=0,02), i.e. the lower was the COX the activity before the treatment, the more prominent syndromes were observed after the treatment.

[The complex neurochemical assessment of brain proteins in mentally healthy subjects and schizophrenic patients].

Relative amounts of the glutamate metabolizing enzymes - glutamine synthetase, glutamine synthetase-like protein, three isoenzymes of glutamate dehydrogenase as well as creatine phosphokinase (a main astroglial energy metabolism enzyme) and major proteins of astro- and oligodendroglia - a glial fibrillary acidic protein and a myelin basic protein were determined in postmortem brain extracts from three areas - the prefrontal cortex, caudate nucleus and cerebellum - from mentally healthy subjects (n=21) and patients with chronic schizophrenia (n=23). To single out "metabolic types" the data obtained have been subjected to cluster analysis. It has been demonstrated for the first time that the cluster analysis of the biological parameters (enzymes and proteins) with correction for age, gender, postmortem interval and presence/absence of diagnosis, enables to distinguish "mentally healthy" cases and "schizophrenic patients" with a high degree of significance (mean mixing error <20%, small er, Cyrillic>>0,00004). Thus, we suppose that mentally healthy controls and patients with schizophrenia are objectively divided into different "metabolic types".

[Glutamate dysmetabolism in patients with schizophrenia].

The glutamate-ergic hypothesis of schizophrenia pathogenesis has been substantially expanded due to recent data on changes in glutamate metabolizing enzymes (GME) in the brain of patients with schizophrenia. Significant changes in the amounts of glutamate synthetase (GS), glutamate synthetase-like protein (GSLP), and glutamate dehydrogenase (GDH) have been found. Alterations in the cerebral metabolism of glutamate (together with disturbances in glutamate receptors and transporters) apparently play an important role in the pathogenesis of schizophrenia. Glutamate dysmetabolism has been shown to be of systemic nature, i.e. the amounts of GME (GDH and GSLP) are elevated in platelets of patients with chronic schizophrenia, and these enzymes may be vital markers of glutamate system status. The amounts of GDH and GSLP were monitored in platelets of chronic patients during treatment with olanzapine, an atypical neuroleptic modulating glutamate concentration in the brain and blood of patients. GSLP amount can serve as a predictor of the duration of treatment to achieve a positive outcome. Further studies of GME in blood may result in elaboration of prognostically valuable biological tests not only for schizophrenia treatments, but also for other mental and nervous system diseases in which the glutamate system is substantially implicated.

[Impaired cerebral glutamate metabolism in mental diseases (Alzheimer's disease, schizophrenia]. / Narushenie metabolizma glutamata v mozge pri psikhicheskoi patologii (bolezn' Al'tsgeimera, shizofreniia).

There is strong evidence for the involvement of the neurotransmitter glutamate system in the pathogenesis of Alzheimer's disease and schizophrenia. In these mental diseases, the brain shows changes in the levels of glutamate and in the function and expression of its transporters and receptors. Since the levels of glutamate are largely determined by the rate of its metabolism, the changes of its concentrations may be associated with dysfunctions of appropriate enzymes. Actually, disturbances of glutamate metabolic enzymes, such as glutaminase, glutamate decarboxylase, and glutamine synthetase were detected in the brain of patients with Alzheimer's disease. The alterations in the expression of glutamine synthetase, glutamine synthetase-like protein, and three isoenzymes of glutamate dehydrogenase in the frontal cortex of patients with schizophrenia suggest that there are impaired glutamate metabolism in this mental disease and Alzheimer's disease.

On the tertiary structure of the Citrus ichangensis satellite DNA.

A hexamer of the repeating unit of Citrus ichangensis satellite DNA was cloned. Polyacrylamide gel electrophoresis demonstrated that the shape of cloned hexamer is other than linear. As the computing of tertiary coordinates made by Eckdahl and Anderson's BEN program proved, the hexamer is a solenoid consisting of two turns termed coiled double helix (CDH)-form. An electron microscopic analysis revealed small diameter circles in the hexamer under investigation. Unlike the hexamer control molecules are s-shaped. It is concluded that the CDH-form is a characteristic of the satellite DNA of Citrus ichangensis.