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There is a progressive trend in the current literature in understanding the central effects of oxytocin, which besides its classical roles in parturition and lactation, seems to exert some facilitatory effects in most of the neuropsychiatric disorders. Thus, it seems that oxytocin is mainly linked to the neuropsychiatric disorders where the social component is more or less affected and it has also strong correlations with the stress-related mechanisms and hypothalamic�pituitary�adrenal (HPA) axis. In addition, the connections between oxytocin and the digestive system were previously suggested, including by some of our preliminary results, in the context of irritable bowel syndrome (IBS) pathology. Also, the relations between depression and stress in the context of cortisol implications are quite well described, although various modifications of cortisol (increased, decreased or non-modified) were described in the major depression pathology. Thus, by using two research cohorts: one with major depression disorder (n = 15) and another one having both diagnosis of major depression disorder and irritable bowel syndrome in the same time (n = 15), we are showing in this report significantly increased levels of cortisol in patients with MDD and IBS, when compared with patients with MDD without IBS, while an opposite pattern was obtained by measuring the plasma level of oxytocin, where the patients with MDD and IBS had a significantly decreased concentration of oxytocin, as compared with those with MDD but without IBS.

The correlations between depression and stress are quite accepted nowadays, as well as the fact that cortisol levels could also represent fundamental risk factors for major depressive disorder. However, when it comes to the modifications of cortisol levels in depression, the results are controversial. Same goes for the cortisol modifications in irritable bowel syndrome (IBS), which is a functional digestive disorder characterized by a strong biopsychological component, being highly influenced or exacerbated by stressful stimuli. Thus, in the present report we were interested in seeing if there are any serum cortisol levels variations in patients with depression and irritable bowel syndrome, by looking at cortisol modifications in two different groups of patients: a control group with major depression disorder and another study group composed by major depression disorder + IBS patients. Thus, our data presented here are suggesting that there is a significant increase in cortisol levels in the morning serum of the patients with major depression disorder + IBS, as compared to the group having only depression. The results presented here could have an important relevance in the context of managing the stress-related factors in the pathological entities described above.

Although the connections between neuropsychiatric and dental disorders attracted the attention of some research groups for more than 50 years now, there is a general opinion in the literature that it remains a clearly understudied and underrated topic, with many unknowns and a multitude of challenges for the specialists working in both these areas of research. In this way, considering the previous experience of our groups in these individual matters which are combined here, we are summarizing in this minireport the current status of knowledge on the connections between neuropsychiatric and dental manifestations, as well as some general ideas on how oxidative stress, pain, music therapy or even irritable bowel syndrome-related manifestations could be relevant in this current context and summarize some current approaches in this matter.

Lately there are increased evidences that oxytocin may be an important mediator in several psychiatric disorders including depression and anxiety. Oxytocin system seems to be linked with several neurotransmitters important in psychiatric disorder, but also with the hypothalamic�pituitary�adrenal (HPA) axis and is also a key factor in stress regulation mechanisms. Considering the oxytocin receptor pattern of distribution both central and peripherally and the growing data concerning the disbalance of oxytocin in psychiatric disorders we may speculate that oxytocin system may be at the core of psychosomatic disturbances. Also, recent data brought to attention that oxytocin receptor is distributed throughout gastrointestinal tract. Our hypothesis of the present study was that oxytocin system is disbalanced in irritable bowel syndrome considering also the psychological component of this digestive disorder. We preliminary report here a significant decrease of serum oxytocin levels in patients with major depression disorder and irritable bowel syndrome, as compared with those with major depression disorder alone.

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. Keywords: Anxiety, Elevated plus maze, Neuropsychiatric diseases, Rat, Social defeat stress, Zebrafish

There is an increased interest in the current literature in how relevant the administration of oxytocin, mostly by using its intranasal administration, could be in some neuropsychiatric disorders and especially in those manifesting a deficit at their sociability level. These aspects made the possible usage of oxytocin as extremely attractive for some management and treatment solutions in the autistic pathology. Thus, we are describing here some original data and current literature status on how oxytocin could help pathophysiological autistic manifestations in both animal models and human patients, by mainly focusing on some specific behavioural or pain manifestations and related oxidative stress status.

Considering the increased awareness on the complex pathophysiological mechanisms associated with irritable bowel syndrome (IBS), a chronic functional dysfunction, defined by a variable pattern of symptoms which can occur both in the small intestine and in the large intestine, in this report we decided to present some original aspects on the less studied and mostly unknown correlations that might exist between irritable bowel syndrome versus sleep patterns and disturbances.

The suicidal behavior is regarded as the act by which a person seeks to take his life, being aware of the consequences of his action. In our review, besides describing the main introductory aspects for the concept of suicide, we focus our attention on the main neurophysiological and genetical mechanisms relevant for this extremely difficult to manage and controversial behavior. Moreover, considering the latest interests in the current literature on the relevance of central oxytocin to various superior cognitive behaviors, we will also make a short description on how important effects of oxytocin could be in the context of suicidal behavior.

In this mini-review we were interested in describing the main genetic, biological and mechanistic aspects of the aggressive behaviour in human patients and animal models. It seems that violent behaviour and impulsive traits present a multifactorial substrate, which is determined by genetic and non-genetic factors. Thus, aggressivity is regulated by brain regions such as the amygdala, which controls neural circuits for triggering defensive, aggressive or avoidant behaviour. Moreover, other brain structures such as the anterior cingulate cortex and prefrontal cortex regions could modulate circuits involved in aggression. Regarding the genetic aspects, we could mention the mutations in the monoamine oxidase or the polymorphisms of the genes involved in the metabolism of serotonin, such as tryptophan hydroxylase. Also, besides the low levels of serotonin metabolites, which seem to be associated with impulsive and aggressive traits, there are good evidences that deficiencies in glutamate transmission, as well as testosterone, vasopressin, hypochloesterolemia or oxytocin modifications could be related to the aggressive behaviour. Regarding oxytocin we present here in the last chapter the controversial results from the current literature regarding the various effects exhibited by oxytocin administration on the aggressive behavior, considering the increased interest in understanding the role of oxytocin on the main neuropsychiatric disorders.

Introduction: Normal aging is characterized by deterioration of visual abilities, affecting mainly visual acuity, contrast and wavelength sensitivity. In the present study we attempted to describe the morphological and morphometric alterations of the dendrites and the dendritic spines of the pyramidal cells of the visual cortex during normal aging, in order to approach the visual impairment of aged individuals from a neuropathological point of view. Material and methods: We studied the visual cortex in 20 brains using the Golgi technique. Results: In pyramidal cells, which represent the majority of cortical neurons, age-related pathology can be observed in cell somata as well as, most importantly, in dendrite number and morphology. The apical dendrites of some pyramidal cells are distorted and tortuous. Horizontal dendritic arborization is also severely decreased. These alterations were more prominent in the corticocortical pyramidal neurons of the 5 th layer. Conclusions: The morphological and morphometric assessment of the dendrites and the dendritic spines in the visual cortex in normal aging revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to visual impairment even in normal aging.

În prezentul articol am fost interesaţi să studiem relevanţa stresului oxidativ în cadrul proceselor legate de abstinenţa de la alcool, având în vedere în special faptul că literatura de specialitate este extrem de controversată în acest domeniu de cercetare. Astfel, am determinat nivelul unor markeri specifici ai stresului oxidativ la pacienţii selectaţi după 3, 6 şi 12 luni de abstinenţă de la alcool. 62 de pacienţi de sex masculin au fost selectaţi pentru studiu. În cadrul studiului s-au prezentat 33 de pacienţi pentru determinările bazale, 14 pacienţi la 3 luni, 14 pacienţi la 6 luni şi 15 pacienţi la 12 luni de abstinenţa de la alcool, în timp ce lotul control a inclus 32 de persoane sănătoase, potrivite ca vârstă si sex-ratio cu celelalte grupuri de studiu. Astfel, în ceea ce priveşte rezultatele, în cazul superoxid dismutazei (SOD) am observat o diferenţă semnificativă între cele trei loturi de studiu (p

In the present report, we studied the associations that might exist between alcohol consumption, cognitive functions and diabetic pathology in patients with type 2 diabetes (T2D). The alcohol intake of 219 patients diagnosed with diabetes was classified into 6 groups: nondrinkers, 0.1-9.9, 10.0-14.9, 15.0-29.9, 30.0-49.9 and ? 50.0, according to the total amount (grams/day) of alcohol consumption. Our results mainly confirm that moderate alcohol consumption can reduce some of the neuropathological aspects of T2D, as demonstrated by the decrease in glycemic levels in patients that consumed higher levels of alcohol (30.0-49.9 g/day), when compared to non-drinkers (p=0.04) or groups in which individuals consumed 0.1-9.9 g/day (p=0.01) and 10.0-14.9 g/day (p=0.02). Regarding the results of cognitive testing, we noticed a significant increase in the values of the MMSE score a lower dose of alcohol intake (0.1-9.9 g/day) was compared with higher doses: 30.0-49.9 g/day (p=0.008) and ? 50.0 g/day (p=0.047).

Different factors seem to contribute to cognitive impairment in the elderly population. It is unclear which cardiovascular risk factors are the most significant contributors to cognitive decline. Although there is some recent neuropathological evidence that vascular lesions and atherosclerotic occlusion of the cerebral arteries may unmask or strengthen the clinical expression of cognitive decline and dementia, there is still little knowledge about the relevance of echocardiographic and arterial stiffness markers as predictors for cognitive decline. In the present study we decided to investigate whether and how the severity of cognitive impairment could be related to cerebral hemodynamic impairment, as well as the possible contribution of the alterations in cerebral hemodynamics (as expressed through some echocardiographic and arterial stiffness markers) to the progression of cognitive decline in a group of patients with cognitive impairments, as compared to a control group with no cognitive deficits. The main finding of our study indicated significant differences in terms of echocardiographic and arterial stiffness markers between the two groups, one composed of patients with cognitive impairment and one with normal-cognitive patients, which suggests an association between these parameters and poor cognitive function. While these functional changes of the cerebral vessel functions could have an important role in the pathogenesis of dementia, the identification of simple and accurate measures that are acceptable to patients and can serve as indicators of current cognitive impairment or the risk of cognitive decline could be very helpful in developing long-term preventive and therapeutic treatments for these patients.

Hypnosis is a widespread technique in psychotherapy with applicability in various psychiatric and psychosomatic disorders. Although there are very few studies in this area of research, some results argue in favor of using hypnosis for various sleep disorders. Insomnia is a common health problem, in both primary form and associated with other pathologies, causing a reduction of self-efficiency/cognitive abilities and an overall decreased life quality. Classical psychotropic medication that is commonly used to treat insomnia can cause significant side effects, produce phenomena of dependence and is generally effective only during the period of treatment. Since the current means of pharmacologic treatment for insomnia present significant limitations, especially when treating chronic insomnia, a more suitable alternative could be attained by non-pharmacological approaches such as hypnosis.

Cardiovascular pathology appears to have a major impact in cognitive decline, and early identification and correction of cardiovascular morbidity could have a major protective impact on cognitive functioning. However, it is not clear how the risk factors for vascular disease can also be risk factors for a general cognitive decline. Regarding cholesterol, its implications in cognitive decline are not very well understood, considering that a high level of cholesterol has been associated with both an increased and decreased risk of dementia. In the present context, we decided to study correlations between cholesterol concentration and the various subdomains of some main psychometric tests, such as MMSE (Mini-Mental State Examination) and MoCA (The Montreal Cognitive Assessment), as well as some measurements for systemic arterial stiffness (brachial and aortic augmentation index) and how they correlate with the aforementioned psychometric parameters. Our results provide additional evidence for a correlation between cholesterol levels and cognitive subdomains (with special focus on orientation, attention, recent memory and long-term memory). Additionally, a significant correlation was found between the brachial and aortic augmentation index and the results of both MMSE and MOCA tests.

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.

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

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 Alzheimer's 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 Alzheimer's 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.

Normal aging is characterized by deterioration of visual abilities, affecting mainly visual acuity, contrast and wavelength sensitivity. In the present study we attempted to describe the morphological and morphometric alterations of the dendrites and the dendritic spines of the pyramidal cells of the visual cortex during normal aging, in order to approach the visual impairment of aged individuals from a neuropathological point of view.We studied the visual cortex in 20 brains using the Golgi technique.In pyramidal cells, which represent the majority of cortical neurons, age-related pathology can be observed in cell somata as well as, most importantly, in dendrite number and morphology. The apical dendrites of some pyramidal cells are distorted and tortuous. Horizontal dendritic arborization is also severely decreased. These alterations were more prominent in the corticocortical pyramidal neurons of the 5th layer.The morphological and morphometric assessment of the dendrites and the dendritic spines in the visual cortex in normal aging revealed substantial alterations of the dendritic arborization and marked loss of the dendritic spines, which may be related to visual impairment even in normal aging.

Oxidative stress may be involved in many somatic and psychiatric pathological states including dementia. The hypothesis of oxidative stress involvement in dementia is supported by much scientific data through biochemical, genetic and molecular studies. Thus, there are many reports of an increased level of the markers for oxidative damage, alterations in the specific activity of the antioxidant system, mutations in specific genes, mitochondrial disturbances and also several connections between oxidative stress and amyloid plaques. Despite these evidence and clinical approaches in using antioxidant therapy in dementia treatment, studies have failed to prove a clear benefit for antioxidant treatment in dementia. Hence, there is a need for further research regarding antioxidant therapy in very early stages of dementia.

s / Parkinsonism and Related Disorders 22 (2016) e149ee192 e183 P 6.034. EXERCISING IS REDUCING ANXIETY, DEPRESSION AND MEMORY DEFICITS INDUCED BY A MPTP-INDUCED RAT MODEL OF PARKINSON'S DISEASE Alin Ciobica , Manuela Padurariu , Radu Lefter , Emil Anton . Alexandru Ioan Cuza University, Iasi, Romania; Gr. T. Popa University, Iasi, Romania; Romanian Academy, Iasi, Romania Objectives: It is well known that in Parkinson's disease (PD) individuals have reductions in physical activity levels, and inactivity is considered an important factor in accelerating the degenerative process of PD. Moreover, PD is known for its cognitive impairments, as well as for depression and anxiety disorders, which may be important causes of morbidity. Also, one of themost used animal models of PD is generated by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: We want it to see if induced physical exercising in an MPTPinduced rat model of PD (20 mg/kg i.p.), will result in any changes in memory (tested in Y-maze), anxiety (tested in elevated-plus-maze) and depression-like behaviour (forced-swim-test), as compared to a nonexercised control group of rats which also received MPTP.The exercising was performed on an adapted treadmill, for 2 weeks (3 series of 5minutes/ day). Results: In the group of exercised MPTP-group we could observe an increased time spent by the rats in the open arms of the elevated-plusmaze, together with a significant decrease of stretching behaviour and increased head dipping, as compared to non-exercised MPTP, suggesting an anxiolytic-like manifestation. In addition, spontaneous alternation in Y maze (index for immediate-memory), and swim-time (anti-depressive index) in forced swim test were increased in the exercised rats with an MPTP-induced model of PD. Conclusions: Physical exercising seems to reduce anxiety, depression and memory deficits associated with a MPTP-induced rat model of PD. P 6.035. COMPUTER AIDED MOVEMENT ANALYSIS OF MPTP MOUSE ON INVERTED HORIZONTAL GRID Wiktor Niewiadomski , Ewelina Palasz , Malgorzata Skupinska , Marek Zylinski , Marta Steczkowska , Anna Gasiorowska , Grazyna Niewiadomska , Gernot Riedel . Mossakowski Institute, Warsaw, Poland; Nencki Institute, Warsaw, Poland; 3 School of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom Objectives: In rodents, the detection and quantification of mouse motor impairment caused by extensive loss of dopaminergic neurons is difficult. The inverted grid test, when mouse moved hanging under the mesh, was believed to be a challenging motor task involving forepaws, which would expose effects of dopaminergic lesions. This assumption was confirmed, however the evaluation of this test relied heavily on subjective rating. Methods: Our aim was to develop an objective method to quantify movement characteristics by limiting the role of rater tomerely identifying the paw position and by performing all subsequent calculation by specifically designed software named “Inverted Mouse”. All calculations are performed by computer yielding holds parameters and parameters of steps. Based on these, number of indices is calculated. Method has been tested in mice with extensive loss of dopaminergic neurons by acute MPTP treatment. Results:With this method it was found that movement characteristics was slightly affected by extensive loss of dopaminergic neurons in substantia nigra. MPTP treated mice performed significantly more forepaws steps and distance covered by forepaws was longer in comparison to controls. Animals rarely performed short lasting touching the wire within the step duration and this occurred almost exclusively in MPTP mice. We revealed and quantified some novel aspects of movement: performing few steps with the same paw, alternating the step length and velocity, relation between the length and velocity of step. Conclusions: We believe, that our method may provide objective measures, not dependent on rater judgment and its results obtained by different researchers may be soundly compared. This work was funded by NCN grant 2011/01/D/NZ7/04405 P 6.037. CROSSBREEDING TWO MICE STRAINS WITH DIFFERENTIAL SUSCEPTIBILITY TO 1-METHYL-4-PHENYL-1,2,3,6TETRAHYDROPYRIDINE (MPTP) POSITIVELY MODULATES NIGRAL DOPAMINERGIC PHENOTYPE D.J. Vidyadhara, H. Yarreiphang, T.R. Raju, Phalguni Anand Alladi. Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India Objectives: To evaluate the phenomenon of differential prevalence of Parkinson's disease (PD) in different ethnic groups and their admixed population, using MPTP mice models. Methods: 15-17weeks adult (n1⁄46) mice from C57BL/6 (MPTP susceptible), CD-1(MPTP resistant) and their reciprocal crossbred strains (F1X1 & F1X2) were studied. Immunohistochemistry for tyrosine hydroxylase (TH) at substantia nigra pars compacta (SNpc) was performed followed by stereological, densitometric and morphological evaluation of dopaminergic (DA) neurons. Western blotting was performed to validate the results. Results: Stereological quantification within SNpc showed significantly higher number of DA neurons in CD-1 and the crossbred mice compared to C57BL/6. Densitometry revealed significantly higher TH expression in the crossbreds compared to parent strains, which was complemented by Western blots. Size of the DA neurons in C57BL/6 was larger and comparable to F1X1, whereas it was smaller in CD-1 and F1X2. Conclusion: Higher nigral DA neuronal numbers in CD-1 mice provides the anatomical evidence for its resistance to MPTP neurotoxicity. As numbers in crossbreds were comparable to CD-1, which is complemented by higher expression of TH, a similar neuroprotectionmay be envisaged for the crossbreds too. Morphological differences in DA neurons may also be a potential susceptibility marker. Thus, the phenomenon of differential susceptibility of mice strains to MPTP and the subsequent crossing provides an interesting experimental paradigm to study the human phenomenon of differential prevalence of PD and its reduced occurrence in admixed population. P 6.038. NIGROSTRIATAL DEGENERATION DICTATES A TOP-DOWN GENETIC PROGRAM FOR NEUROPLASTICITY AND NEUROREPAIR: FOCUS ON THE HIPPOCAMPUS AND WNT/GSK-3b/b-CATENIN SIGNALING CASCADE Bianca Marchetti , Francesca L'Episcopo , Cataldo Tirolo , Nunzio Testa , Maria Francesca Serapide . OASI Inst. for Res and Care (IRCCS), Neuropharmacol. Section; Dept. of Biomed. and Biotechnol Sci., Pharmacology Univ. of Catania Medical School, 94018 Troina (EN) and 95125, Catania, Italy; OASI Inst. for Res and Care (IRCCS), Neuropharmacol. Section, 94018 Troina, EN, Italy; OASI Inst. for Res and Care (IRCCS), Neuropharmacol. Section, 94018 Troina, EN, Italy; Dept. of Biomed. and Biotechnol Sci., Physiology Sections, Univ. of Catania Medical School, 95125 Catania, Italy Objectives: Canonical Wnt/bcatenin signaling chiefly regulates dopaminergic (DA) neurodevelopment, hippocampal neurogenesis and synaptic plasticity. We have provided substantial evidence that timely activation of endogenous Wnt/b-catenin signaling within and outside the neurogenic niches promotes an intrinsic compensatory program leading to histopathological and functional nigrostriatal DA neurorepair in the MPTP model of Parkinson's disease (PD) (1-3). Here, we investigated the response of the hippocampal dentate gyrus (DG) where the disruption of the DA balance in the hippocampus inhibits neurogenesis in and this may be crucial for the clinical neurological and cognitive deficits observed in PD. Methods: We used Wild type (Wt) and transgenic (Tg) b-catenin reporter mice receiving the PD neurotoxin, MPTP; qPCR coupled to immunohistochemistry to correlate the hipocampal gene expression signature with protein distribution at different time-intervals after injury. Results: We herein identified a timeand injury-dependent downand up-modulation of Wnt signaling transcripts associated to significant

It is believed that in Alzheimer's disease (AD) some areas of the brain are particularly vulnerable to specific degenerative processes and that they could exhibit neuronal dysfunction in the earliest stage of the disease. The implications of the hippocampus in memory processes are very well known and it is likely that the hippocampus would be among the first areas of the brain affected by the pathogenic mechanisms occurring in AD. However, the distinction between the neurodegenerative changes that accompany normal ageing and those that characterize AD is not clear. Also, the distribution of the hippocampal cell loss in both normal aging and AD is not very well understood.In this context, we focused on the quantification of the neuronal density in the four specific areas of the hippocampus (CA1-CA4) of AD brains, as compared to an age-matched control group, by using the Nissl staining technique.We found a significant reduction of neuronal density especially in the CA1 and CA3 hippocampal areas. The most prominent decrease was found at the CA1 area level, as compared to all other 3 areas which were analyzed.In the present study we managed to demonstrate and confirm a significant neuronal loss of hippocampus in AD, as compared to an age-matched control group. Moreover, it seems that this decrease of hippocampal neuronal density is more prominent especially at the CA1 and also in the CA3 hippocampal areas. This could have important implications in the design of therapeutic and investigative strategies of AD. However, larger samples are necessary in order to provide the basis for firmer conclusions in this area of research.

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.

We determined the specific activities of some enzymatic antioxidant defenses like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as a lipid peroxidation marker (MDA-malondialdehyde) from the serum of patients with schizophrenia treated with typical and atypical antipsychotics, in comparison with a normal age- matched control group. We observed an increased oxidative stress in schizophrenic patients treated with typical antipsychotics, compared to controls. Moreover, we demonstrated an antioxidant effect of atypical antipsychotics, since these patients showed an increased activity of SOD, compared to control subjects and a slightly decrease of MDA

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 arm-maze, 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.

One of the most widely used animal models of Parkinson’s disease (PD) involves injecting 6-hydroxydopamine (6-OHDA) directly into the substantia nigra (SN). Some recent reports speculated that dopaminergic drugs may exert brain antioxidant activity, which could explain some of their protective actions. In this way, the aim of the present study was to examine the effects of low-dose pergolide on memory deficits and brain oxidative stress in a 6-OHDA-induced rat model of PD. Right-unilateral lesions of the SN were produced with 6-OHDA. Two weeks after neurosurgery, pergolide (0.3 mg/kg/day) was injected intraperitoneally in the 6-OHDA + pergolide and sham-operated + pergolide groups, while sham-operated and 6-OHDA alone groups received saline. Radial-8-arm maze and Y-maze were used for memory assessment. We also determined some enzymatic antioxidant defenses like superoxide dismutase or glutathione peroxidase and a lipid peroxidation marker [malondialdehyde (MDA)], from the temporal lobe. A reduced number of working/reference memory errors was observed in 6-OHDA + pergolide group, compared to sham-operated rats. Additionally, post hoc analysis showed significant differences between 6-OHDA and 6-OHDA + pergolide groups in both Y-maze and radial-arm-maze tasks. We also noted a significant decrease of MDA level in the 6-OHDA + pergolide group, compared to sham-operated rats. Significant correlations were also found between behavioral parameters and MDA levels. Our data suggest that pergolide facilitates spatial memory and improves brain oxidative balance, after a 6-OHDA-induced model of PD. This could be useful for further investigations and clinical applications of pergolide.

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.