Manuela Padurariu

Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimers disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimers disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.

Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics

Studies performed in schizophrenia patients have generally suggested the presence of a compromised antioxidant system, but this is not always consistent with specific observed parameters, which on the whole, show evidences of dysregulation. There are also controversies regarding the oxidative stress status in patients treated with typical vs. atypical antipsychotics. In this context, the aim of the present work was to evaluate the specific activity of some peripheral antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the level of a lipid peroxidation maker (malondialdehyde-MDA), in schizophrenic patients treated with typical (haloperidol) or atypical (olanzapine, quetiapine and risperidone) antipsychotics, compared with age-matched healthy subjects. We found a significant decrease in GPX specific activity and also a significant increase of MDA levels in schizophrenic patients, compared to age-matched control group, regardless of their type of treatment. Additionally, an increase in SOD specific activity was observed, mainly in the patients treated with haloperidol and quetiapine. Further research is necessary in order to elucidate the effects of different antipsychotic agents on antioxidant enzymes and lipid peroxidation or possible interventions at the oxidative stress level in schizophrenic patients.

Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders

PURPOSE We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8μg/3μl and 16μg/3μl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress. MATERIAL/METHODS Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase. RESULTS 5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations. CONCLUSION 5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.

Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat

In addition to its known classical roles, the renin angiotensin system (RAS) has more subtle functions which include the regulation of emotional responses. Previous studies regarding the anxiety related behavior of RAS have showed controversial results. There is also evidence that oxidative stress accompanies angiotensin II infusion, but the role of AT1/AT2 specific receptors is not clear. The aim of this study was to evaluate the effects of central angiotensin II receptor blockers on anxiety state and oxidative stress. Behavioral testing included elevated plus maze, while oxidative stress status was measured though the extent of a lipid peroxidation product (malondialdehyde-MDA) and the specific activity of some defense antioxidant enzymes (superoxide dismutase-SOD and glutathione peroxidase-GPx). The rats treated with angiotensin II spent significantly less time in the open-arms of elevated-plus-maze, while the administration of losartan resulted in a significant increase of this time. We observed a significant increase of MDA concentration in the angiotensin II group and a decrease of MDA levels in both losartan and PD-123177 groups. In addition, a significant correlation was seen between the time spent in the open arms and oxidative stress markers. These findings could lead to important therapeutic aspects regarding the use of angiotensin II receptor blockers in anxiety-related disorders.

The interdependence of the reactive species of oxygen, nitrogen, and carbon.

This mini-review tries to summarize the main interdependences between the free radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for these radical species are described, as well as how these affect their interaction and functional implications. Emphasis is made on the metabolic disturbances induced by stressing aggressions that produce radical species. In this way, cellular oxidative imbalances created by the superiority of reactive oxygen species over the antioxidant systems produce both activation of nitroxide synthases and the oxidation of terminal nitrogen from l-arginine, as well as the metabolization of heme until carbon monoxide by nitric oxide-activated hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations determined by these three kinds of radical species are completed by the involvement of hydrogen sulfide, which results from the degradation of l-cysteine by cistationine-γ-lyase. In this way, sufficient experimental data tend to demonstrate the involvement of hydrogen sulfide and other thiol derivatives in the interrelations between oxygen, nitrogen, and carbon, which results in a true radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic stress, may constitute a central point where other factors of vulnerability meet, and their interactions could have an important impact in many modern diseases. Considering that the actions of reactive species can be most of the time corrected, future studies need to establish the therapeutical importance of various agents which modulate oxidative, nitrosative, or carbonilic stress.

Inhibition of Central Angiotensin Converting Enzyme Exerts Anxiolytic Effects by Decreasing Brain Oxidative Stress

Inhibition of Central Angiotensin Converting Enzyme Exerts Anxiolytic Effects by Decreasing Brain Oxidative Stress This study investigated the effects of angiotensin II and captopril intracerebroventricular administration on anxiety status and brain oxidative stress. Elevated plus maze was used in order to asses the anxiety-like behavior, while the biochemical analysis included the determination of some antioxidant defense enzymes like superoxide dismutase and glutathione peroxidase and also a lipid peroxidation product (malondialdehyde). Our results provide additional evidence of angiotensin II induced anxiety-like effects and increased prooxidant status. Moreover, the blockade of angiotensin II, by the administration of an angiotensin converting enzyme inhibitor (captopril) resulted in anxiolytic effects and decreased oxidative stress status. In addition, we found a significant correlation between the time spent by rats in the open arms of the elevated plus maze and oxidative stress markers. This could raise important therapeutic issues regarding the anxiolytic effects of some angiotensin converting enzyme inhibitors used primarily for hypertension, such as captopril. Also, it seems that oxidative stress could play an important part in these actions. Inhibicija Centralnog Enzima Koji Konvertuje Angiotenzin Deluje Kao Anksiolitik Smanjujući Oksidativni Stres u Mozgu Ispitivan je uticaj intracerebroventrikularne administracije angiotenzina II i kaptoprila na napetost i oksidativni stres u mozgu. Za procenjivanje ponašanja bliskog anksioznosti korišćen je test uzdignutog lavirinta u obliku znaka plus, dok je biohemijska analiza obuhvatila određivanje nekih enzima antioksidantne odbrane kao što su superoksid-dismutaza i glutation-peroksidaza i proizvoda lipidne peroksidacije (malondialdehid). Naši rezultati predstavljaju još jedan dokaz da angiotenzin II izaziva posledice nalik na anksioznost i povišen prooksidantni status. Štaviše, blokiranje angiotenzina II davanjem inhibitora enzima koji konvertuje angiotenzin (kaptoprila) delovalo je kao anksiolitik i dovelo do sniženja statusa oksidativnog stresa. Pored toga, otkrivena je značajna korelacija između vremena koje su pacovi proveli u otvorenim »rukama« lavirinta i markera oksidativnog stresa. Ovo možda ukazuje na važnost pokretanja nekih važnih terapijskih pitanja koja se tiču anksiolitičkog dejstva nekih inhibitora enzima koji konvertuju angiotenzin a koji se pre svega koriste za hipertenziju, kakav je kaptopril. Takođe, sva je prilika da oksidativni stres u tome igra važnu ulogu.

Describing some behavioural animal models of anxiety and their mechanistics with special reference to oxidative stress and oxytocin relevance

Abstract It is now generally accepted that animal studies are playing an important role in the understanding of anxiety disorders, since they contribute to the current knowledge regarding the mechanisms and possible therapeutic approaches in anxiety. In the present review we will detail some essential aspects of behavioral animal models of anxiety related to social defeat paradigm, elevated plus maze, elevated zero or T maze, light/dark box, social interaction test or tests based on predator models, considering the latest theories and methodological approaches in this area of research, as well as our previous studies focusing on anxiety manifestations in a variety of species including rats, zebrafish, dogs and pigs. Moreover, in this context, we will focus on the recent theories concerning oxidative stress, as well as importance of oxytocin administration (especially the intranasal route). This could be important considering that these two factors are currently being investigated as possible mechanisms (oxidative stress status) and related therapeutic target (both intranasal oxytocin and antioxidants) in the pathology of the anxiety disorders.

General issues encountered while diagnosing mild cognitive impairment in Romanian patients: Mild cognitive impairment in Romanian patients

Mild cognitive impairment (MCI) could be defined as a transition phase between normal aging and dementia. If one can imagine a scale of cognitive continuum, which has normal aging and dementia as benchmarks, MCI would be somewhere between the two, represented by cognitive disorders, which do not interfere significantly with one individual’s social or occupational functionality (Petersen et al., 1999). The main objective of this study is to validate Montreal Cognitive Assessment (MoCA) in Romanian language. MoCA is an instrument for screening cognitive function and has already been translated in 46 languages. MoCA has been validated by means of comparison, by placing the test in parallel with a similar one that has already been translated in Romania—mini-mental state examination (MMSE).

The effects of angiotensin II and angiotensin 1-7 in cognitive processes and oxidative stress in rats. Relevance for Alzheimer's disease

(VROI). Hippocampal and dorsolateral frontal (DLFC) cortex VROIs were selected from the SPM sub-utility ‘Pickatlas’. In each subject, mean FDG uptake values within VROIs was computed using Mask subtool of SPM and normalized to the cerebellar uptake. Both in patients and controls, normalized VROI values were used as dependent variables in multiple regression analyses to search for metabolic correlations (connectivity) with the whole brain (uncorrected p < 0.001 at peak level and p < 0.05 FDR-corrected at cluster level). Correlation analysis was repeated in an independent group of 69 healthy subjects.Results:As compared to controls, pAD showed relative hypometabolism in precuneus, posterior cingulate gyrus and superior parietal lobule in both hemispheres. This hypometabolic area showed less metabolic connectivity in pAD with respect to CTR (autocorrelation versus wide correlation with temporal and frontal lobes, respectively). PAD showed limited correlation even innon-hypometabolic areas. Both hippocampi showed correlation with controlateral homologues only, while in CTR correlation was highlighted with precuneus/ posterior cingulate and frontal cortex. Similarly, DLFC correlation was limited to ipsilateral frontal cortex, while involving caudate nuclei and parietal cortex in CTR. Results in CTR were confirmed in the wider sample of 69 subjects. Conclusions: Metabolic connectivity is impaired in pAD. The reduced metabolic connections both in hypometabolic and non-hypometabolic areas suggest that metabolic disconnection (possible sign of degeneration at synaptic level) may antedates hypometabolism (early sign of neuronal death).

Modulation of the acetylcholine-catecholamine balance in the cognitive processes and its correlations with the oxidative stress

Background Impairments of cognitive performance have been observed our previous studies in normal rats with muscarinic acethylcholine receptors (mAchRS), beta-adrenergic receptors (β AR) and D2-dopamine receptors (D2R) blockade, suggesting that these receptors have a facilitator role in learning and memory processes. Learning and memory processes are coordinated with different brain regions [1]. Since the oxidative damage may play a role in the aging process [2], including the associated decline, age-related impairment in spatial learning and memory may be alleviated by antioxidant treatment [3].