Synaptic dysfunction in schizophrenia.

Schizophrenia is a chronic disease presented with psychotic symptoms, negative symptoms, impairment in the reward system, and widespread neurocognitive deterioration. Disruption of synaptic connections in neural circuits is responsible for the disease's development and progression. Because deterioration in synaptic connections results in the impaired effective processing of information. Although structural impairments of the synapse, such as a decrease in dendritic spine density, have been shown in previous studies, functional impairments have also been revealed with the development of genetic and molecular analysis methods. In addition to abnormalities in protein complexes regulating exocytosis in the presynaptic region and impaired vesicle release, especially, changes in proteins related to postsynaptic signaling have been reported. In particular, impairments in postsynaptic density elements, glutamate receptors, and ion channels have been shown. At the same time, effects on cellular adhesion molecular structures such as neurexin, neuroligin, and cadherin family proteins were detected. Of course, the confusing effect of antipsychotic use in schizophrenia research should also be considered. Although antipsychotics have positive and negative effects on synapses, studies indicate synaptic deterioration in schizophrenia independent of drug use. In this review, the deterioration in synapse structure and function and the effects of antipsychotics on the synapse in schizophrenia will be discussed.

Telomeres and Psychological Stress: Perspective on Psychopathologies.

Introduction: Telomeres are specialized DNA-protein complexes located at the ends of all chromosomes and act as a "molecular clock" to determine the replicative lifespan of the cells. Recent studies indicate that life-long exposure to stress, starting from the prenatal period, causes many diseases to emerge at an early age, and telomeres may be possible mediators in this process. This article aims to review the relationship between the stress-telomere-disease triad and the potential role of telomere dysfunction in psychopathologies in the light of current literature. Methods: A literature search was conducted along the lines of a narrative review. PubMed and Web of Science databases were used to identify all types of articles published from inception to January 2022. After the title/abstract search, articles available in full text and English were selected based on key findings, the applicability of the method used to test the hypothesis, limitations, interpretation of the results, and impact of the results in the field. A total of 73 records were included in this narrative review. Results: The fact that some age-related chronic diseases, such as cardiovascular diseases and type 2 diabetes, are seen more frequently and at an earlier age in certain psychopathologies including depression, bipolar disorder, and schizophrenia suggests that these disorders are premature ageing syndromes. Although there are some conflicting results in the literature, in line with this hypothesis, the presence of shortened telomeres reported in these psychopathologies and the impact of lifelong exposure to stress on this process are remarkable. Conclusion: Many of the studies point to an association and do not tell much about the causality. Hence, the elucidation of the biological processes underlying the relationship between psychological stress, dysfunctional telomeres and complex, common age-related diseases, as well as psychiatric disorders is important and further studies are needed at the cellular level.

LRP5-linked osteoporosis-pseudoglioma syndrome mimicking isolated microphthalmia.

Microphthalmia is defined as the measurement of the total axial length of the eyeball to be below average of the two standard deviation according to the age. While several genes have been identified so far related to microphthalmia, the genetic etiology of the disease has not been fully understood because of genetic heterogeneity observed in this disease. After exclusion of the genes that had been known to be the cause of microphthalmia, we performed homozygosity mapping and exome sequencing to clarify the genetic etiology of the bilateral microphthalmia in this family. When the results of the exome and microarray data were considered together as a splice-site mutation in LRP5 gene [c.2827 + 1G > A], which is known to be important for eye development and Wnt receptor signaling pathway, was found to be the cause of microphthalmia in our family. It was understood that after finding this mutation, when bone mineral density was measured with DXA in the family whose ages range between 19 and 28 and who have no bone problem before, osteoporosis was diagnosed. It was also understood that microphthalmia found in this family is a clinical finding of OPPG syndrome.

Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys.

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. alpha-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.