Inhibitors of Endocannabinoids' Enzymatic Degradation as a Potential Target of the Memory Disturbances in an Acute N-Methyl-D-Aspartate (NMDA) Receptor Hypofunction Model of Schizophrenia in Mice.

Treating schizophrenia with the available pharmacotherapy is difficult. One possible strategy is focused on the modulation of the function of the endocannabinoid system (ECS). The ECS is comprised of cannabinoid (CB) receptors, endocannabinoids and enzymes responsible for the metabolism of endocannabinoids (fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL)). Here, the aim of the experiments was to evaluate the impact of inhibitors of endocannabinoids' enzymatic degradation in the brain: KML-29 (MAGL inhibitor), JZL-195 (MAGL/FAAH inhibitor) and PF-3845 (FAAH inhibitor), on the memory disturbances typical for schizophrenia in an acute N-methyl-D-aspartate (NMDA) receptor hypofunction animal model of schizophrenia (i.e., injection of MK-801, an NMDA receptor antagonist). The memory-like responses were assessed in the passive avoidance (PA) test. A single administration of KML-29 or PF-3845 had a positive effect on the memory processes, but an acute administration of JZL-195 impaired cognition in mice in the PA test. Additionally, the combined administration of a PA-ineffective dose of KML-29 (5 mg/kg) or PF-3845 (3 mg/kg) attenuated the MK-801-induced cognitive impairment (0.6 mg/kg). Our results suggest that the indirect regulation of endocannabinoids' concentration in the brain through the use of selected inhibitors may positively affect memory disorders, and thus increase the effectiveness of modern pharmacotherapy of schizophrenia.

Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands.

The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long-term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain.

The Influence of an Acute Administration of Cannabidiol or Rivastigmine, Alone and in Combination, on Scopolamine-Provoked Memory Impairment in the Passive Avoidance Test in Mice.

Memory is one of the most important abilities of our brain. The process of memory and learning is necessary for the proper existence of humans in the surrounding environment. However, sometimes there are unfavourable changes in the functioning of the brain and memory deficits occur, which may be associated with various diseases. Disturbances in the cholinergic system lead to abnormalities in memory functioning and are an essential part of clinical symptoms of many neurodegenerative diseases. However, their treatment is difficult and still unsatisfactory; thus, it is necessary to search for new drugs and their targets, being an alternative method of mono- or polypharmacotherapy. One of the possible strategies for the modulation of memory-related cognitive disorders is connected with the endocannabinoid system (ECS). The aim of the present study was to determine for the first time the effect of administration of natural cannabinoid compound (cannabidiol, CBD) and rivastigmine alone and in combination on the memory disorders connected with cholinergic dysfunctions in mice, provoked by using an antagonist of muscarinic cholinergic receptor-scopolamine. To assess and understand the memory-related effects in animals, we used the passive avoidance (PA) test, commonly used to examine the different stages of memory. An acute administration of CBD (1 mg/kg) or rivastigmine (0.5 mg/kg) significantly affected changes in scopolamine-induced disturbances in three different memory stages (acquisition, consolidation, and retrieval). Interestingly, co-administration of CBD (1 mg/kg) and rivastigmine (0.5 mg/kg) also attenuated memory impairment provoked by scopolamine (1 mg/kg) injection in the PA test in mice, but at a much greater extent than administered alone. The combination therapy of these two compounds, CBD and rivastigmine, appears to be more beneficial than substances administered alone in reducing scopolamine-induced cognitive impairment. This polytherapy seems to be favourable in the pharmacotherapy of various cognitive disorders, especially those in which cholinergic pathways are implicated.

Epilepsy in Pediatric Patients-Evaluation of Brain Structures' Volume Using VolBrain Software.

Epilepsy is one of the most frequent serious brain disorders. Approximately 30,000 of the 150,000 children and adolescents who experience unprovoked seizures are diagnosed with epilepsy each year. Magnetic resonance imaging is the method of choice in diagnosing and monitoring patients with this condition. However, one very effective tool using MR images is volBrain software, which automatically generates information about the volume of brain structures. A total of 57 consecutive patients (study group) suffering from epilepsy and 34 healthy patients (control group) who underwent MR examination qualified for the study. Images were then evaluated by volBrain. Results showed atrophy of the brain and particular structures-GM, cerebrum, cerebellum, brainstem, putamen, thalamus, hippocampus and nucleus accumbens volume. Moreover, the statistically significant difference in the volume between the study and the control group was found for brain, lateral ventricle and putamen. A volumetric analysis of the CNS in children with epilepsy confirms a decrease in the volume of brain tissue. A volumetric assessment of brain structures based on MR data has the potential to be a useful diagnostic tool in children with epilepsy and can be implemented in clinical work; however, further studies are necessary to enhance the effectiveness of this software.

Effects of Fatty Acid Amide Hydrolase Inhibitors Acute Administration on the Positive and Cognitive Symptoms of Schizophrenia in Mice.

The connection between the endocannabinoid system (ECS) and schizophrenia is supported by a large body of research. The ECS is composed of two types cannabinoid (CB: CB1 and CB2) receptors and their endogenous ligands, endocannabinoids. The best-known endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are intracellularly degraded by fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Thus, the function of ECS might be modulated in a direct way, through CB receptor ligands or indirectly by FAAH and MAGL inhibitors. We evaluated that the direct influence of ECS, using FAAH (URB 597) and MAGL (JZL 184) inhibitors, on the schizophrenia-like effects in mice. The behavioral schizophrenia-like symptoms were obtained in animals by using N-methyl D-aspartate (NMDA) receptor antagonists, MK-801. An acute administration of MK-801 (0.3 and 0.6 mg/kg) induced psychotic symptoms in rodents, manifested as the increase in locomotor activity, measured in actimeters, as well as the memory impairment, assessed in the passive avoidance (PA) task. We revealed that an acute administration of URB 597, at the dose of 0.3 mg/kg, attenuated MK-801 (0.6 mg/kg)-induced memory impairment. In turn, an acute administration of URB 597 at a higher dose (1 mg/kg) potentiated MK-801 (0.3 mg/kg)-induced memory impairment. Similarly, an acute administration of JZL 184 (20 and 40 mg/kg) intensified an amnestic effect of MK-801 (0.3 mg/kg). Moreover, an acute injection of JZL 184 (1 mg/kg) potentiated hyperlocomotion is provoked by MK-801 (0.3 and 0.6 mg/kg) administration. The present findings clearly indicate that ECS, through an indirect manner, modulates a variety of schizophrenia-like responses in mice.

Intima-media complex thickness and carotid atherosclerotic plaque formation in Lublin's population in the context of selected comorbidities.

INTRODUCTION: Atherosclerosis (arteriosclerosis) is a chronic arterial disease of the arteries with chronic inflammatory. The pathology of atherosclerosis is complex, and the atherosclerotic process is multi-factorial, not fully understood. Risk factors of atherosclerotic lesions may include: lipid disorders, hypertension or diabetes. One of the diagnostic methods of discovering atherosclerosis covers the assessment of the intima-media complex thickness by Doppler ultrasonography. AIM: The aim of this report was an evaluation of the relationships between intima-media complex thickness in the right and left carotid arteries and the occurrence of atheromatous plaque in the Lublin population with respect to three possible concomitant medical conditions, mentioned above. MATERIAL AND METHODS: A group of 121 subjects was included into the study, all of the participants being residential inhabitants of the Lublin Voivodship. All the participating patients were requested to fill in a questionnaire. After that, the patients were submitted to Doppler sonography concentrated on intima-media complex thickness evaluation. The occurrence of atheromatous plaque was also assessed in obtained sonographic images. RESULTS: There were statistically significant differences for the intima-media complex thickness and for the atheromatous plaque according to all of the reported diseases: hypocholesterolaemia, hypertension and diabetes. Conclusions: The present study confirms that there is a relationship between the thickness of the intima-media complex in the right and left carotid arteries as well as the occurrence of the atherosclerotic plaque regarding the coexistence of specific disease entities in the subjects of the Lublin population.

Sonographic assessment of the prevalence and evolution of fluid collections as a complication of kidney transplantation.

AIM OF THE STUDY: The aim of this study is to assess the prevalence and evolution of perirenal fluid collections in a group of 488 patients who have undergone kidney transplantation. MATERIAL AND METHODS: Sonographic documentation of 488 deceased-donor kidney recipients was evaluated for the prevalence of perirenal fluid collections and their evolution in time, depending on selected demographic features of the patients, time of detection, initial dimensions and precise position of the collection relative to the kidney and the location of the transplanted organ in the right or left iliac fossa. The collected data were used for statistical analysis to determine the strength of the potential relationships. RESULTS: In 146 out of 488 subjects perirenal fluid collections were found. In 1/3 of the patients more than one fluid collection was diagnosed. Over 40% of fluid collections were detected within 10 days from the date of the first scan and 24.11% were detected within 10-20 days from the date of the first scan. The majority of fluid collections were located near the lower pole of the kidney. Perihilar collections were the least common. Collections encapsulating the kidney and subcutaneous collections were the largest in size on average. A statistically significant difference between the size of collections located on the surface and the size of those located near the upper pole of the transplanted kidney was demonstrated. However, no correlation was proven to exist between the persistence of the fluid collection and its position relative to the transplanted kidney and its initial size. CONCLUSIONS: The correct evaluation of a fluid collection's dynamics of development and nature requires periodic follow-up of the recipient, preferably in a single clinical center. Ultrasonography is an inexpensive, non-invasive and repeatable method for the determination of the presence of fluid collections. However, the decision whether treatment is necessary requires the sonographic image to be compared with the laboratory signs of inflammation and biochemical analysis of the contents of fluid collections.

The Influence of the CB1 Receptor Ligands on the Schizophrenia-Like Effects in Mice Induced by MK-801.

A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders. For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms. The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia. We provoked psychosis-like effects in mice by an acute administration of NMDA receptor antagonist, MK-801 (0.1-0.6 mg/kg). An acute administration of MK-801 induced psychotic symptoms, manifested in the increase in locomotor activity (hyperactivity), measured in actimeters, as well as the memory impairment, assessed in the passive avoidance task. We revealed that an acute injection of CB1 receptor agonist, oleamide (5-20 mg/kg), had no influence on the short- and long-term memory-related disturbances, as well as on the hyperlocomotion in mice, provoking by an acute MK-801. In turn, an amnestic effects or hyperactivity induced by an acute MK-801 was attenuated by an acute administration of AM 251 (0.25-3 mg/kg), a CB1 receptor antagonist. The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice. Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.