Aldehyde dehydrogenase 2 in sporadic Parkinson's disease.

Aldehyde dehydrogenases (ALDH) play a key role in neuronal protection. They exert this function by metabolizing biogenic amine-related aldehydes, e.g. 3,4-dihydroxyphenylacetaldehyde (DOPAL), and by protecting neurons against aldehyde- and oxidative stress-related neurotoxicity. The role of these different isoenzymes has been discussed in other neurodegenerative disorders before. It is somewhat surprising that only few studies have investigated their role in the aetiology of Parkinson's disease (PD), in both the degeneration of dopaminergic neurons and the formation of Lewy bodies. Earlier studies report severe alterations of the cytosolic isoform of ALDH expression (ALDH 1A1) in the substantia nigra of patients with PD. However, there are no data regarding the activity of ALDH 2 located at the inner mitochondrial membrane. Since mitochondrial dysfunctions are hypothesized to be of importance in the aetiology of PD we have examined the enzymatic activity of mitochondrial ALDH 2 in post-mortem putamen and frontal cortex of patients with PD and controls. We found that mitochondrial ALDH 2 activity in contrast to the frontal cortex was significantly increased in the putamen of patients with PD compared to controls.

Accessibility, standards and challenges of electroconvulsive therapy in Western industrialized countries: a German example.

OBJECTIVES: The aim of the study was to document the present situation of electroconvulsive therapy (ECT) in Germany, compare its handling with regard to other industrialized countries and with regard to a survey 12 years ago. METHODS: A questionnaire on the frequency and type of administration of ECT in 2008 was sent electronically to 423 psychiatric hospitals. As needed, up to five reminders were carried out by telephone. On this occasion, the question of whether ECT is administered, could be clarified for each hospital. RESULTS: A total of 43% (183/423) of hospitals declared to administer ECT; 63% (115/183) reported nearly 20,000 treatments. A total incidence of 30,000 treatments performed on 2800 individual patients was estimated. This means that 3.4 patients per 10(5) inhabitants, 0.4‰ of all depressed patients, and about 1% of depressed inpatients, are treated with ECT in Germany. CONCLUSIONS: The frequency of application has increased during the last 12 years by a factor of more than 2.5 in Germany. In Western industrialized countries, numbers vary by a factor of more than 10 amongst the countries with a slow trend of equalization. The mode of implementation and the areas of conflict in which the therapy stands seem to be similar.

Alteration of the pro-oxidant xanthine oxidase (XO) in the thalamus and occipital cortex of patients with schizophrenia.

OBJECTIVES: Mounting evidence shows that oxidative stress (OS) and the purine/adenosine system play a key role in the pathophysiology of schizophrenia. Lately, our group pointed out that not only antioxidants, but also the prooxidant system plays an important role in neuro-psychiatric disorders. Xanthine oxidase (XO) is an enzyme of special interest in this context, since it acts as a prooxidant, but its main product is a vastly important antioxidant, uric acid (UA). Furthermore, XO plays major part in the purine/adenosine metabolism, which has been hypothesised to play a role in schizophrenia as well. METHODS: We examined the activity of XO in the striato-cortico-limbic system of schizophrenic patients (SP) and controls using a commercially available activity assay. RESULTS: We found decreased activity of XO in the occipital cortex and thalamus of patients with psychosis. Furthermore, XO shows a significant positive correlation with chlorpromazine equivalents in the putamen and the temporal cortex. CONCLUSIONS: Nevertheless, our results might suggest a downregulation of cellular defence mechanisms in schizophrenia in several brain regions, which could account for neuronal alterations which have been described before. This demonstrates that more research is needed to fully understand the role of the complex enzyme XO in the pathophysiology of schizophrenia.

Can enzyme kinetics of prooxidants teach us a lesson about the treatment of Alzheimer's disease: a pilot post-mortem study.

OBJECTIVES: Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue. METHODS: We determined the Michaelis-Menten constant (K(M)) and the maximal velocity (V(Max)) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays. RESULTS: We found the Michaelis-Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters. CONCLUSIONS: These results add further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD.

Increased xanthine oxidase in the thalamus and putamen in depression.

A growing body of literature suggests persistent and selective structural changes in the cortico-limbic-thalamic-striatal system in patients with recurrent depressive disorder (DD). Oxidative stress is thought to play a key role in these processes. So far, the main scientific focus has been on antioxidant enzymes in this context. For the first time, this proof of concept study examines the activity of the free radicals producing the enzyme, xanthine oxidase (XO), directly in the cortico-limbic-thalamic-striatal system of patients with recurrent depression. The activity of XO was ascertained in the cortico-limbic-thalamic-striatal regions in post-mortem brain tissue of patients with recurrent depressive episodes and individuals without any neurological or psychiatric history (7/7). We measured the XO activity in following brain areas: hippocampus, regio entorhinalis, thalamus, putamen and caudate nucleus. In this study, we report a significant increase of XO activity in the thalamus and the putamen of patients with depression. Our findings contribute to the growing body of evidence suggesting that oxidative stress plays a pivotal role in certain brain areas in recurrent depressive disorder.

Increased activity of mitochondrial aldehyde dehydrogenase (ALDH) in the putamen of individuals with Alzheimer's disease: a human postmortem study.

For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD.