Romeo Dobrin

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.

Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context.

The Relevance of Oxidative Stress Status in One Week and One Month Alcohol Abstinent Patients

Abstract Background: Although it is generally accepted that there is an increased oxidative stress status in alcoholics, the separate relevance of oxidative stress following alcohol withdrawal is still not understood to this date. There are reports stating that the increased oxidative stress status in alcoholics may persist independently of the constant presence of alcohol intake, while on the other side, it was demonstrated that the antioxidant defense mechanism could significantly increase after alcohol withdrawal. Methods: In the present work, we were interested in studying the relevance of oxidative stress status in the alcohol withdrawal processes, by determining some oxidative stress markers (two antioxidant enzymes: superoxide dismutase - SOD and glutathione peroxidase - GPX and a lipid peroxidation maker - MDA) after one week and one month of abstinence, as compared to the baseline and a control group of subjects. Results: Our data confirmed the increased oxidative stress status in alcoholic patients and, more importantly, we de m - onstrated here a significant decrease of the oxidative stress status one week and one month following the withdrawal, as showed by a significant increase in the specific activity of SOD (p<0.003), as well as by a decrease in MDA levels (p<0.019). Still, in the case of all three markers of oxidative stress status which we determined, the levels after one week or one month of abstinence were significantly altered when compared to controls. Conclusions: This suggests that severe and prolonged deficiency in the oxidative stress marker levels needs longer than one month of abstinence to normalize. Kratak sadržaj Uvod: lako je poznato da kod alkoholičara postoji stanje po- jačanog oksidativnog stresa, do sada nije zasebno utvrđena važnost oksidativnog statusa u apstinenciji. Neki izveštaji go- vore da stanje povišenog oksidativnog stresa kod alkoholi- čara može trajati nezavisno od stalnog unosa alkohola, dok je s druge strane pokazano da mehanizam antioksidantne odbrane može značajno ojačati posle prestanka konzumira- nja alkohola. Metode: U ovom radu nas je zanimalo da proučimo važnost statusa oksidativnog stresa u procesima odvikavanja od alko- hola, putem određivanja nekih od markera oksidativnog stre- sa (dva antioksidantna enzima: superoksid-dismutaze - SOD i glutation-peroksidaze - GPX, kao i markera lipidne peroksi- dacije - MDA) posle nedelju dana i posle mesec dana apsti- nencije i poređenja sa nivoima na početku studije i u kontrol- noj grupi ispitanika. Rezultati: Naši podaci potvrđuju postojanje pojačanog oksi- dativnog stresa kod alkoholičara. Štaviše, pokazali smo ovde da posle nedelju i posle mesec dana apstinencije dolazi do značajnog smanjenja oksidativnog stresa, koje se ogleda u značajnom porastu specifične aktivnosti SOD (p< 0,003) kao i sniženju nivoa MDA (p<0,019). Ipak, u slučaju tri markera statusa oksidativnog stresa koje smo odredili, nivoi posle ne- delju i posle mesec dana apstinencije bili su značajno izme- njeni u poređenju sa kontrolnom grupom. Zaključak: Ovo ukazuje da je potrebno više od mesec dana apstinencije kako bi se normalizovala ozbiljna i produžena deficijencija u nivoima markera oksidativnog stresa.

PRELIMINARY DATA ON SOME BEHAVIORAL CHANGES INDUCED BY SHORT-TERM INTRAPERITONEAL OXYTOCIN ADMINISTRATION IN AGED RATS

INTRODUCTION Oxytocin (OT) is a well-known neuropeptides which together with vasopressin, melatonin, insulin and other hormones can alter both behavior and physiological or neuronal functions. This growing interest on OT roles is also based on the demonstrated beneficial effects as a stress reliever and a social bonding agent. The association between old age and OT was only vaguely studied. Little or few is known on the effect of the OT hormone on the old body. Hereby, we present our preliminary results in the research on behavioral changes regarding the intraperitoneal administration of OT in aged rats. SUBJECTS AND METHODS OT was administered for 8 days in Wistar aged rats in parallel with saline administration for control group. Behavioral markers were assessed in some specific behavioral tasks, such as the Y-Maze test for short-term working memory, Open Field test, Elevated Plus Maze, and Forced Swim test for anxious and depressive behavior assessment, and Three-chambered Maze test for sociability assessment. RESULTS Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT). Similarly, significant differences were obtained regarding the social behavior of the intraperitoneal OT-treated animal as compared to control group, the animals showing increased sociability and social preference for the stranger animal in TCT. However, no significant effects on the working memory (assessed as spontaneous alternation in YMT) were observed. CONCLUSIONS Intraperitoneal administration of OT in aged rats has clear effects on anxious and depressive behavior, but no significant effects on the working memory. Also, several beneficial effects of OT on social preferences and sociability were observed.