Evaluation of the Therapeutical Effect of Matricaria Chamomilla Extract vs. Galantamine on Animal Model Memory and Behavior Using 18F-FDG PET/MRI.

The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia.

The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. Methods: We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. Results: The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Conclusions: Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

Cognitive Impairment following Mild Traumatic Brain Injury (mTBI): A Review.

Background: Mild Traumatic Brain Injury (mTBI) has been increasingly recognized as a public health concern due to its prevalence and potential to induce long-term cognitive impairment. We aimed to consolidate this observation by focusing on findings of neuropsychological assessments, neuroimaging, risk factors, and potential strategies for intervention to prevent and treat mTBI-associated cognitive impairments. Methods: A thorough search of PubMed, PsycINFO, and Embase databases was performed for studies published until 2024. Studies focusing on cognitive impairment after mTBI, with neurocognitive assessment as a primary outcome, were included. Results: We found consistent evidence of cognitive deficits, such as memory and attention impairments, and affected executive functions following mTBI. Neuroimaging studies corroborate these findings, highlighting structural and functional changes in the brain. Several risk factors for developing cognitive impairment post-mTBI were identified, including age, gender, genetics, and pre-existing mental health conditions. The efficacy of interventions, including cognitive rehabilitation and pharmaceutical treatment, varied across studies. Conclusions: Mild TBI can lead to significant long-term cognitive impairments, impacting an individual's quality of life. Further research is necessary to validate and standardize cognitive assessment tools post-mTBI, to elucidate the underlying neural mechanisms, and to optimize therapeutic interventions.

The Effects of Transcranial Direct Current Stimulation in Patients with Mild Cognitive Impairment.

Transcranial direct current stimulation (tDCS) came into consideration in recent years as a promising, non-invasive form of neuromodulation for individuals suffering from mild cognitive impairment (MCI). MCI represents a transitional stage between normal cognitive aging and more severe cognitive decline, which appears in neurodegenerative diseases, such as Alzheimer's disease. Numerous studies have shown that tDCS can have several useful effects in patients with MCI. It is believed to enhance cognitive functions, including memory and attention, potentially slowing down the progression of neurodegeneration and cognitive decline. tDCS is believed to work by modulating neuronal activity and promoting synaptic plasticity in the brain regions associated with cognition. Moreover, tDCS is generally considered safe and well-tolerated, making it an attractive option for long-term therapeutic use in MCI. However, further research is needed to determine the optimal stimulation parameters and long-term effects of tDCS in this population, as well as its potential to serve as a complementary therapy alongside other interventions for MCI. In this review, we included 16 randomized clinical trials containing patients with MCI who were treated with tDCS. We aim to provide important evidence for the cognitive enhancement using tDCS in patients with MCI, summarizing the effects and conclusions found in several clinical trials, and discuss its main mechanisms.

Metacognition in Schizophrenia Spectrum Disorders-Current Methods and Approaches.

Metacognition essentially represents "thinking about thinking", or the individual's capacity to control and monitor their own cognitive processes. Metacognition impairment in schizophrenia represents a core feature of the disease, and, in the last fifteen years, the subject has evolved into a growing study area concentrating on a wide variety of processes, such as clinical insight, autobiographical memory, cognitive beliefs, reasoning, and memory biases. Since metacognition is a complex subject, we wanted to focus on the different nuances of metacognition transposed into the lives of patients diagnosed with either schizophrenia or a schizoaffective disorder. Therefore, this narrative review aims to analyze the literature in order to provide an insight regarding the current methods and approaches in the study of metacognition in schizophrenia or schizoaffective disorders, as well as the results provided. Results from the reviewed studies showed that patients with schizophrenia have a lower metacognitive ability, which is strongly reflected in their lives. Studies to date have highlighted the interaction between schizophrenia symptoms and metacognition, which shows how metacognition impacts work performance, autobiographical memory, motivation, the severity of symptoms, and social cognition.

The Quest for Neurodegenerative Disease Treatment-Focusing on Alzheimer's Disease Personalised Diets.

Dementia represents a clinical syndrome characterised by progressive decline in memory, language, visuospatial and executive function, personality, and behaviour, causing loss of abilities to perform instrumental or essential activities of daily living. The most common cause of dementia is Alzheimer's disease (AD), which accounts for up to 80% of all dementia cases. Despite that extensive studies regarding the etiology and risk factors have been performed in recent decades, and how the current knowledge about AD pathophysiology significantly improved with the recent advances in science and technology, little is still known about its treatment options. In this controverted context, a nutritional approach could be a promising way to formulate improved AD management strategies and to further analyse possible treatment strategy options based on personalised diets, as Nutritional Psychiatry is currently gaining relevance in neuropsychiatric disease treatment. Based on the current knowledge of AD pathophysiology, as well as based on the repeatedly documented anti-inflammatory and antioxidant potential of different functional foods, we aimed to find, describe, and correlate several dietary compounds that could be useful in formulating a nutritional approach in AD management. We performed a screening for relevant studies on the main scientific databases using keywords such as "Alzheimer's disease", "dementia", "treatment", "medication", "treatment alternatives", "vitamin E", "nutrition", "selenium", "Ginkgo biloba", "antioxidants", "medicinal plants", and "traditional medicine" in combinations. Results: nutrients could be a key component in the physiologic and anatomic development of the brain. Several nutrients have been studied in the pursuit of the mechanism triggered by the pathology of AD: vitamin D, fatty acids, selenium, as well as neuroprotective plant extracts (i.e., Ginkgo biloba, Panax ginseng, Curcuma longa), suggesting that the nutritional patterns could modulate the cognitive status and provide neuroprotection. The multifactorial origin of AD development and progression could suggest that nutrition could greatly contribute to the complex pathological picture. The identification of adequate nutritional interventions and the not yet fully understood nutrient activity in AD could be the next steps in finding several innovative treatment options for neurodegenerative disorders.

Carob Seed Peels Effect on Cognitive Impairment and Oxidative Stress Status in Methionine-Induced Mice Models of Schizophrenia.

Background:Ceratonia siliqua L. (Carob tree) is a Mediterranean evergreen, well known for its medicinal properties. The different parts of Carob were proven to exert antidiabetic, antibacterial, antifungal, and antiproliferative effects. Hence, the present paper aims to validate the positive correlation between the high antioxidant activity of carob seed peels and the improvement of negative symptoms of schizophrenia. Materials & Methods: The antioxidant activity was carried out using the ß-carotene test. Methionine and carob seed peels (CSP) extracts (50 and 100 mg/kg) were orally administrated to mice for a week. After administration, behavioral tests were assessed using the Y-maze, elevated plus maze, and forced swimming tests, as well as the novel object recognition task. Furthermore, the oxidative stress status was evaluated by analyzing the levels of the antioxidant enzymes: Superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde levels (MDA). Results: Both extracts exhibited remarkable antioxidant activity and showed antibacterial effect against Gram-positive bacteria tested (Bacillus subtilis and Staphylococcus aureus) and against Pseudomonas aeruginosa (Gram-negative). Therefore, Escherichia coli was very resistant. The behavioral tests proved the efficacy of CSP in enhancing the cognitive impairment of animal models of schizophrenia. Hence, the stated correlation between oxidative stress and schizophrenia was confirmed by the increased SOD and GPx activities and the decreased MDA level. Conclusions: The present study gave further confirmation of the potential correlation between oxidative stress and the development of psychiatric disorders and highlighted the use of natural antioxidants, especially Ceratonia siliqua L. in the improvement of cognitive impairment in the dementia of schizophrenia.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.

Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish-Focussing on Neurobehavioural and Psychological Responses.

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species.

Oxytocin: Narrative Expert Review of Current Perspectives on the Relationship with Other Neurotransmitters and the Impact on the Main Psychiatric Disorders.

Is a cyclic neuropeptide produced primarily in the hypothalamus and plays an important neuromodulatory role for other neurotransmitter systems, with an impact on behavior, response to danger, stress, and complex social interactions, such as pair bonding and child care. This narrative expert review examines the literature on oxytocin as a brain hormone. We focused on oxytocin structure, distribution, genetics, and the oxytocin receptor system, as well as the relationship of oxytocin with other neurotransmitters and the resulting impacts on the main psychiatric disorders. Oxytocin levels have been correlated over time with mental illness, with numerous studies focusing on oxytocin and the pathophysiology of the main psychiatric disorders, such as autism, schizophrenia, personality disorders, mood, and eating disorders. We highlight the role oxytocin plays in improving symptoms such as anxiety, depression, and social behavior, as the literature suggests. Risk factors and causes for psychiatric disorders range from genetic to environmental and social factors. Oxytocin could impact the latter, being linked with other neurotransmitter systems that are responsible for integrating different situations during the development phases of individuals. Also, these systems have an important role in how the body responds to stressors or bonding with others, helping with the creation of social support groups that could speed up recovery in many situations. Oxytocin has the potential to become a key therapeutic agent for future treatment and prevention strategies concerning the main psychiatric disorders.

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson's Disease Chronically Exposed to Rotenone.

Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson's disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood−brain barrier (BBB) and accumulates in mitochondria. Unfortunately, most of the existing data focus on locomotion. This is why the present study aimed to bring novel evidence on how ROT alone or in combination with different potential ant(agonists) might influence the social and aggressive behavior using the counterclockwise rotation as a neurological pointer. Material and Methods: Thus, we exposed zebrafish to ROT­2.5 µg/L, valproic acid (VPA)­0.5 mg/mL, anti-parkinsonian drugs (LEV/CARB)­250 mg + 25 mg, and probiotics (PROBIO)­3 g for 32 days by assessing the anti-social profile and mirror tests and counterclockwise rotation every 4 days to avoid chronic stress. Results: We observed an abnormal pattern in the counterclockwise rotation only in the (a) CONTROL, (c) LEV/CARB, and (d) PROBIO groups, from both the top and side views, this indicating a reaction to medication and supplements administered or a normal intrinsic feature due to high levels of stress/anxiety (p < 0.05). Four out of eight studied groups­(b) VPA, (c) LEV/CARB, (e) ROT, and (f) ROT + VPA­displayed an impaired, often antithetical behavior demonstrated by long periods of time on distinct days spent on the right and the central arm (p < 0.05, 0.005, and 0.0005). Interestingly, groups (d) PROBIO, (g) ROT + LEV/CARB, and (h) ROT + PROBIO registered fluctuations but not significant ones in contrast with the above groups (p > 0.05). Except for groups (a) CONTROL and (d) PROBIO, where a normalized trend in terms of behavior was noted, the rest of the experimental groups exhibited exacerbated levels of aggression (p < 0.05, 0.005, and 0.001) not only near the mirror but as an overall reaction (p < 0.05, 0.005, and 0.001). Conclusions: The (d) PROBIO group showed a significant improvement compared with (b) VPA, (c) LEV/CARB, and ROT-treated zebrafish (e−h). Independently of the aggressive-like reactions and fluctuations among the testing day(s) and groups, ROT disrupted the social behavior, while VPA promoted a specific typology in contrast with LEV/CARB.

Post-Concussion Syndrome and Chronic Traumatic Encephalopathy: Narrative Review on the Neuropathology, Neuroimaging and Fluid Biomarkers.

Traumatic brain injury is a significant public health issue and represents the main contributor to death and disability globally among all trauma-related injuries. Martial arts practitioners, military veterans, athletes, victims of physical abuse, and epileptic patients could be affected by the consequences of repetitive mild head injuries (RMHI) that do not resume only to short-termed traumatic brain injuries (TBI) effects but also to more complex and time-extended outcomes, such as post-concussive syndrome (PCS) and chronic traumatic encephalopathy (CTE). These effects in later life are not yet well understood; however, recent studies suggested that even mild head injuries can lead to an elevated risk of later-life cognitive impairment and neurodegenerative disease. While most of the PCS hallmarks consist in immediate consequences and only in some conditions in long-termed processes undergoing neurodegeneration and impaired brain functions, the neuropathological hallmark of CTE is the deposition of p-tau immunoreactive pre-tangles and thread-like neurites at the depths of cerebral sulci and neurofibrillary tangles in the superficial layers I and II which are also one of the main hallmarks of neurodegeneration. Despite different CTE diagnostic criteria in clinical and research approaches, their specificity and sensitivity remain unclear and CTE could only be diagnosed post-mortem. In CTE, case risk factors include RMHI exposure due to profession (athletes, military personnel), history of trauma (abuse), or pathologies (epilepsy). Numerous studies aimed to identify imaging and fluid biomarkers that could assist diagnosis and probably lead to early intervention, despite their heterogeneous outcomes. Still, the true challenge remains the prediction of neurodegeneration risk following TBI, thus in PCS and CTE. Further studies in high-risk populations are required to establish specific, preferably non-invasive diagnostic biomarkers for CTE, considering the aim of preventive medicine.

The Possible Role of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 on Locomotor Activity and Oxidative Stress in a Rotenone-Induced Zebrafish Model of Parkinson's Disease.

BACKGROUND: As every organ within the body, the brain is also extremely susceptible to a plethora of noxious agents that change its chemistry. One component frequently found in current products against harmful species to crops is rotenone whose effect under prolonged exposure has been demonstrated to cause neurodegenerative disorders such as Parkinson's disease. The latest reports have indeed revealed that rotenone promotes Parkinson's in humans, but studies aiming to show congruent effects in zebrafish (Danio rerio) are lacking. Material and Methods. In this context, the aim of the present study was to demonstrate how chronic administration of rotenone for 3 weeks impairs the locomotor activity and sociability and induces oxidative stress in zebrafish. RESULTS: There were no statistically significant differences following the analysis of their social interaction and locomotor tests (p > 0.05). However, several exceptions have been noted in the control, rotenone, and probiotics groups when we compared their locomotor activity during the pretreatment and treatment interval (p < 0.05). We further assessed the role of rotenone in disturbing the detoxifying system as represented by three enzymes known as superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Despite the fact that there were no statistically significant changes within SOD and GPx levels between the control group and rotenone, probiotics, and rotenone + probiotics (p > 0.05), relevant changes have been observed between the analyzed groups (p < 0.05 and p < 0.005, respectively). On the other hand, significant differences (p < 0.05) have been observed for MDA when we analyzed the data between the control group and the other three groups. CONCLUSIONS: Our results suggest that rotenone can be successfully used to trigger Parkinson's disease-related symptomatology in zebrafish.

Cortisol and Oxytocin Could Predict Covert Aggression in Some Psychotic Patients.

Background: The covert or indirect type of aggression has a risk of converting in violent acts and, considering that, it is very important to identify it in order to apply effective preventive measures. In cases of psychotic patients, the risk of becoming violent is harder to predict, as even neuter stimuli may be perceived as threat and trigger aggression. Treating all the psychiatric patients as potential aggressive subjects is not the best preventive measure as only a few of them are aggressive and this measure may further enhance the stigma on mentally ill patients. There is a current need for better understanding of covert aggression and to find objective measures, such as biological markers, that could be indicative of potential violent behavior. In this work, we try to investigate the role of cortisol and oxytocin as potential biomarkers of aggression in patients with psychosis. Material and Methods: We analyzed the level of peripheral oxytocin (pg/mL) and cortisol level (ng/mL) in 28 psychotic patients (they were not on psychotropic treatment at the moment of admission and those with substance abuse or personality disorder were excluded from the study) and correlated it with the intensity of aggression reported by the patient (overt and covert type) using the Overt Covert Aggression Inventory and the level of observed aggression of the patient in the past 7 days (rated by the health care provider) using the Modified Overt Aggression Scale. Results: We found that psychotic patients with a higher level of covert aggression had a lower level of cortisol (61.05 ± 8.04 ng/mL vs. 216.33 ± 12.6.9 ng/mL, p ˂ 0.01) and a higher level of oxytocin (102.87 ± 39.26 vs. 70.01 ± 25.07, p = 0.01) when compared with patients with a lower level of covert aggression. Furthermore, we observed significant negative correlation between cortisol and covert aggression (r = -0.676, p < 0.001) and between oxytocin and covert type of aggression (r = 0.382, p = 0.04). Moreover, we found that a lower level of cortisol together with a higher level of oxytocin are significant predictors of a style of internalized manifestation of aggression, with the predictive model explaining 55% of the variant of the internalized manifestation of aggression (F (2.25) = 17.6, p < 0.001, ß = 0.35, R2 = 55.2). We did not find significant correlations between cortisol and overt aggression, and neither between oxytocin and overt aggression. Positive correlations were also found between the overt type of self-reported aggression and overt aggression reported by the rater (r = 0.459, p = 0.01). Conclusions: The importance of a predictive model in understanding covert aggression is imperative and the results of our study show that oxytocin and cortisol warrant to be further investigated in establishing a definitive predictive model for covert aggression.

Morphological alterations of the pyramidal and stellate cells of the visual cortex in schizophrenia.

Schizophrenia is a severe brain disorder characterized by certain types of delusion, hallucination and thought disorder. Studies have revealed impaired synaptic plasticity and reduced gamma-aminobutyric acid levels of the visual cortex in patients with schizophrenia. While previous work established a critical role for interneurons and cortical connectivity in the generation of hallucinations, the present study set out to examine the morphology of pyramidal cells and interneurons from layers 3 and 4 in the primary visual cortex from schizophrenic brains and to identify any dendritic and spinal alterations in comparison to normal control brains. The morphological and morphometric changes of the pyramidal cells and the interneurons of the visual cortices of 10 brains obtained from patients with schizophrenia, in comparison to 10 age-matched controls, were studied using the Golgi method and 3D neuronal reconstruction techniques. Analysis using the Golgi impregnation technique revealed a significant loss of distal dendritic segments, tortuous branches and varicosities and an overall restriction of the dendritic field in the brains of schizophrenic patients in both pyramidal cells and in aspiny interneurons. The present results may explain certain clinical phenomena associated with the visual cortex usually encountered in schizophrenia.

A Voxel-Wise Meta-Analysis on the Cerebellum in Essential Tremor.

Background and Objectives: Essential tremor is a chronic progressive neurological condition. The clinical presentation of essential tremor is heterogeneous and includes involuntary tremor on hands or arms and progressively on head, jaw, and voice. More extensive and complex symptoms may also be noticed in several patients. Many studies have been carried out to identify biomarkers to help the diagnosis, however, all the efforts have not shown any substantial results yet. Materials and Methods: Here, we aimed to perform a voxel-based meta-analysis using a dedicated cerebellar mask to clarify whether the results from the previous studies are robust and have any clinical significance. We included studies with a total of 377 essential tremor patients and 338 healthy control individuals. Results: A significant regional decrease in the volume of the gray matter was detected in the right cerebellar hemispheric lobule IV/V, and in the cerebellar vermic lobule IV/V. Conclusions: This is the first study focused on the cerebellum and using a specific cerebellar mask, which increases the sensitivity. It showed regional statistically significant changes that could not be seen in the whole-brain analysis.

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.

Preliminary Data on the Interaction between Some Biometals and Oxidative Stress Status in Mild Cognitive Impairment and Alzheimer's Disease Patients.

Increased interest regarding the biometal mechanisms of action and the pathways in which they have regulatory roles was lately observed. Particularly, it was shown that biometal homeostasis dysregulation may lead to neurodegeneration including Alzheimer's disease, Parkinson disease, or prion protein disease, since important molecular signaling mechanisms in brain functions implicate both oxidative stress and redox active biometals. Oxidative stress could be a result of a breakdown in metal-ion homeostasis which leads to abnormal metal protein chelation. In our previous work, we reported a strong correlation between Alzheimer's disease and oxidative stress. Consequently, the aim of the present work was to evaluate some of the biometals' levels (magnesium, manganese, and iron), the specific activity of some antioxidant enzymes (superoxide dismutase and glutathione peroxidase), and a common lipid peroxidation marker (malondialdehyde concentration), in mild cognitive impairment (n = 15) and Alzheimer's disease (n = 15) patients, compared to age-matched healthy subjects (n = 15). We found increased lipid peroxidation effects, low antioxidant defense, low magnesium and iron concentrations, and high manganese levels in mild cognitive impairment and Alzheimer's disease patients, in a gradual manner. These data could be relevant for future association studies regarding the prediction of Alzheimer's disease development risk or circling through stages by analyzing both active redox metals, oxidative stress markers, and the correlations in between.

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.