The neural cell adhesion molecule and synaptic plasticity

Highly stereotyped patterns of neuronal connections are laid down during the development of the nervous system via a range of activity independent and activity dependent mechanisms. Whereas the coarse hard-wiring of the nervous system appears to rely on molecular recognition events between the neuron, its pathway, and its target, the establishment of precisely patterned functional circuits is thought to be driven by neuronal activity. In this review we discuss the role that the neuronal cell adhesion molecule (NCAM) plays in morphological plasticity. Recent studies on NCAM and its probable species homologue in Aplysia (apCAM) suggests that an individual CAM can function to both promote synaptic plasticity and maintain the structure of the synapse. In the adult brain, changes between stability and plasticity are likely to underlie dynamic morphological changes in synaptic structures associated with learning and memory. In this review we use NCAM as an example to illustrate mechanisms that can change the function of an individual CAM from a molecule that promotes plasticity to one that does not. We also discuss evidence that NCAM promotes plasticity by activating a conventional signal transduction cascade, rather than by modulating adhesion perse. Finally, we consider the evidence that supports a role for NCAM in learning and memory. © 1995 John Wiley & Sons, Inc.     

The Lean Woman

Objective: In the current obesity epidemic, the ability to remain lean is beginning to be uncommon. Therefore, it was considered of interest to characterize such subjects. Research Methods and Procedures: From a population of premenopausal women (n = 270), all 40 years of age, those with a similar body mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1 kg/m²) were selected among nonsmokers and compared with the remaining nonsmoking women. Results: Lean women showed, as expected, low waist-to-hip circumference ratio and abdominal sagittal diameter as well as absence of other disease risk factors. Compared with the remaining women, 17β-estradiol was high and androgens were low, whereas insulin-like growth factor I and thyroid hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin hormone were not different. Results from questionnaires indicated higher education and socioeconomic status, frequent sports activities, and better psychosocial adaptation and psychological health. A tetranucleotide repeat polymorphism in the fifth intron of the aromatase P450 gene was longer among the lean (187 base pairs) than the rest of the women. Women with opposite phylogenetic characteristic have a short microsatellite (168 base pairs) in this gene locus. Discussion: Lean, nonsmoking women enjoy an excellent health in not only anthropometric and metabolic factors, but also in neuroendocrine, endocrine, and psychological variables. The endocrine measurements suggest a well-functioning aromatase, which in turn might have a genetic background, contributing to health. The aromatase gene might be important for regulation of body fat mass.     

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue‐Specific Inducer

A large number of studies have focused on the generation of dopaminergic neurons from pluripotent cells. Differentiation of stem cells into distinct cell types is influenced by tissue‐specific microenvironment. Since, central nervous system undergoes further development during postnatal life, in the present study neonatal rat brain tissue extract (NRBE) was applied to direct the differentiation of embryonal carcinoma stem cell line, P19 into dopaminergic (DA) phenotypes. Additionally, a neuroprotective drug, deprenyl was used alone or in combination with the extract. Results from morphological, immunofluorescence, and qPCR analyses showed that during a period of one to three weeks, a large percentage of stem cells were differentiated into neural cells. The results also indicated the greater effect of NRBE on the differentiation of the cells into tyrosine hydroxylase‐expressing cells. MS analysis of NRBE showed the enrichment of gene ontology terms related to cell differentiation and neurogenesis. Network analysis of the studied genes and some DA markers resulted in the suggestion of potential regulatory candidates such as AVP, ACHE, LHFPL5, and DLK1 genes. In conclusion, NRBE as a natural native inducer was apparently able to simulate the brain microenvironment and support neural differentiation of P19 cells.     

The relationship between sperm DNA fragmentation,free radicals and antioxidant capacity with idiopathic repeated pregnancy loss

More than two consecutive miscarriages in less than 20 weeks of gestation is defined as recurrent spontaneous miscarriage. Various causes such as uterine anatomical anomalies, genetic factors, and infectious and endocrine disorders have been reported for RPL. However, approximately 50% of the causes are unknown, which can be due to male factors. Several studies have been done on semen parameters to determine the unknown causes and risk factors for miscarriages, however, only studying common semen parameters have not been sufficient. In this study, the relationship between sperm DNA fragmentation, the amount of free radicals, and total antioxidant capacity (TAC) in semen have been considered as a risk factor for spontaneous miscarriage. Semen samples were collected from 42 men whose partners had a history of spontaneous miscarriage and 42 fertile men as the control group. Volume, pH, viscosity, concentration, and motility of semen, as well as sperm morphology were measured. Sperm DNA fragmentation was analyzed by the sperm chromatin structure assay (SCSA) and TUNEL methods, the amount of sperm free radicals was measured by the luminescence method and the total amount of semen antioxidant was measured using the TAC kit. The results have shown that sperm motility in the experimental group was significantly less than the control group (P?=?0.001). The percentage of sperm DNA fragmentation and the amount of free radicals in the experimental group were significantly higher than the control group (P?<?0.001). The total amount of antioxidant was lower in the experimental group compared to the control. Spouses of men with lower sperm motility and higher DNA fragmentation had a higher chance of spontaneous miscarriage when compared to the control group. The results of this study support the hypothesis that sperm DNA fragmentation is a major contributor to spontaneous miscarriage.The relationship between SDF, ROS and TAC with RPL.     

Anticonvulsant Activity and Toxicity of Essential Oil and Methanolic Extract of Zhumeria majdae Rech, a Unique Iranian Plant in Mice

Drug-resistance and adverse effects of current drugs are the most obstacles in the treatment of epilepsy. In a plan for finding new natural anticonvulsant agents, we studied the anticonvulsant effects of essential oil (ZMEO) and methanolic extract (ZMME) of Zhumeria majdae in pentylene tetrazol (PTZ) and maximal electro-shock (MES) models in mice. Mice received different doses of ZMEO and ZMME, 30?min before induction of chemical and electrical convulsions. Neurotoxicity (movement toxicity and sedation) was evaluated using rota-rod test. The mortality was determined after 24?h following injection of different doses of the ZMEO and ZMME. The obtained results show that ZMEO dose-dependently protected mice from tonic convulsions induced by PTZ and MES with effective doses (ED₅₀) of 0.26 (0.13?C0.39) and 0.27 (0.17?C0.37)?ml/kg respectively. Toxic doses (TD₅₀) in rota-rod test for ZMEO was 0.55 (0.42?C0.70)?ml/kg. ZMME at dose of 2?g/kg decreased tonic convulsions as much as 40?%. For ZMEO, TD₅₀ of 0.55 (0.45?C0.69)?ml/kg was obtained. ZMME significantly decreased the walking time in rota-rod test at dose of 2?g/kg. Lethal dose (LD₅₀) of ZMEO was determined as 2.35 (1.98?C2.65)?ml/kg. ZMME showed about 34?% death of the animals at dose 5?g/kg. The essential oil of Z. majdae could be a good candidate for further anticonvulsive studies.     

Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood–brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6?nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.     

Vitamin K series: current status and future prospects

The Vitamin K series, particularly menaquinone, have been attracting research attention, due to the potential in reducing both osteoporosis and cardiovascular diseases. This review provides an overview of the types of vitamin K and their health benefits. This is followed by a critical review of the various biotechnological approaches used in the production of menaquinone, including solid and liquid state fermentations, extraction and recovery. The currently available market information is summarized and future growth prospects are discussed. Recommendations are also given for areas of future research in order to improve the production process for menaquinone and reduce costs.