The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship.

Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia-C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p<0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p>0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p<0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p<0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p>0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.

Papel del factor neurotrófico de origen cerebral y de la neurotropina-3 en la relación de Chlamydophila pneumoniae con la esquizofrenia / The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship

Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in response to various manifestations of infection. Therefore, we aimed to elucidate the roles of BDNF and NT3 in the schizophrenia-C. pneumoniae infection relationship. RT-PCR, immunofluorescence and ELISA methods were used. Fifty patients suffering from schizophrenia and 35 healthy individuals were included as the patient group (PG) and the healthy control group (HCG), respectively. We detected persistent infection in 14 of the 50 individuals in the PG and in 1 of the 35 individuals in the HCG. A significant difference was found between the two groups (p < 0.05). Twenty-two individuals in the PG and 13 in the HCG showed seropositivity for past C. pneumoniae infection, and no difference was observed between the groups (p > 0.05). C. pneumoniae DNA was not detected in any group. A significant difference in NT-3 levels was observed between the groups, with very low levels in the PG (p < 0.001). A significant difference in BDNF levels was also found, with lower levels in the PG (p < 0.05). The mean serum NT-3 level was higher in the PG cases with C. pneumoniae seropositivity than in seronegative cases; however, this difference was not statistically significant (p > 0.05). In conclusion, we suggest that NT-3 levels during persistent C. pneumoniae infection may play a role in this relationship.

Existe la sospecha de que algunos patógenos pueden desempeñar un papel en la patogénesis de la esquizofrenia; en ese contexto, se ha propuesto que la infección persistente causada por células de Chlamydophila pneumoniae presentes en las células endoteliales cerebrales durante muchos años lleva a la inflamación crónica. Recientemente se ha planteado la hipótesis de que el factor neurotrófico de origen cerebral (BDNF, por sus siglas en inglés) y la neurotropina-3 (NT-3) podrían estar implicados en el desarrollo de la esquizofrenia, y se ha sugerido que sus niveles se modifican en respuesta a diversas manifestaciones de la infección. En esta investigación intentamos esclarecer el papel que desempeñan el BDNF y la NT3 en la relación entre la esquizofrenia y la infección por C. pneumoniae. Se utilizaron métodos de RT-PCR, inmunofluorescencia y ELISA. Se incluyeron 50 pacientes con esquizofrenia y 35 individuos sanos como grupo de pacientes (GP) y grupo de controles sanos (GCS), respectivamente. Detectamos una infección persistente en 14 sujetos del GP y en 1 de los del GCS, lo que constituyó una diferencia significativa (p < 0,05). Veinte participantes del GP y 13 del GCS fueron seropositivos para una infección pasada por C. pneumoniae, diferencia no significativa (p > 0,05). No se detectó ADN de C. pneumoniae en ninguno de los dos grupos. Se observó una diferencia significativa entre los grupos en los niveles de NT-3, que fueron muy bajos en el GP (p < 0,001), y de BDNF, inferiores en el GP (p < 0,05). La concentración sérica media de NT-3 fue mayor en los individuos seropositivos para C. pneumoniae en comparación con los seronegativos, pero esta diferencia no alcanzó significación estadística (p > 0,05). Sugerimos que los niveles de NT-3 durante una infección persistente por C. pneumoniae pueden estar implicados en la relación de Chlamydophila pneumoniae con la esquizofrenia.

Alzheimer's disease and epigenetic diet.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Many efforts have been directed to prevent AD due to its rising prevalence and the lack of an effective curative treatment. Various epigenetic mechanisms are linked to pathogenesis of AD. Epigenetic alterations may occur through external factors and are known for their reversibility. Dietary factors can influence epigenetic mechanisms. Several neuroprotective nutrients have been shown to enhance cognition, memory and other impaired functions seen in AD. Within recent years neuroprotective nutrients have gained more attention in the field of epigenetic. A growing body of evidence suggest that epigenetic changes triggered by dietary nutrients have an important role in health and in prevention of some diseases, especially neurodegenerative disorders. Several studies have shown that folic acid, vitamin B12, choline, zinc, selenium, dietary polyphenols are capable of interacting with epigenetic mechanisms and ultimately gene expression. Epigenetic mechanisms resulting in neuronal dysfunction may be modified by diet. Therefore manipulation of epigenetic mechanisms via dietary nutrients may affect influence the vulnerability of neurons to degeneration which is seen in AD. The aim of this article is to provide a brief overview about the recent findings related to epigenetic alterations that are linked to AD pathogenesis, and to discuss the bioactive nutrients which can affect these epigenetic mechanisms.

Medical radiation exposure and human carcinogenesis-genetic and epigenetic mechanisms.

Ionizing radiation (IR) is a potential carcinogen. Evidence for the carcinogenic effect of IR radiation has been shown after long-term animal investigations and observations on survivors of the atom bombs in Hiroshima and Nagasaki. However, IR has been widely used in a controlled manner in the medical imaging for diagnosis and monitoring of various diseases and also in cancer therapy. The collective radiation dose from medical imagings has increased six times in the last two decades, and grow continuously day to day. A large number of evidence has revealed the increased cancer risk in the people who had frequently exposed to x-rays, especially in childhood. It has also been shown that secondary malignancy may develop within the five years in cancer survivors who have received radiotherapy, because of IR-mediated damage to healthy cells. In this article, we review the current knowledge about the role of medical x-ray exposure in cancer development in humans, and recently recognized epigenetic mechanisms in IR-induced carcinogenesis.

Determination of binding points of methylene blue and cationic phenoxazine dyes on human butyrylcholinesterase.

In this study, the binding points of MethB and two structurally-related cationic phenoxazine dyes [meldola blue (MB) and nile blue (NB)] to human butyrylcholinesterase (BChE) were investigated by molecular docking and site directed mutagenesis. The comparative inhibitory effects of MethB, MB and NB on recombinant wild type BChE and six human BChE mutants were spectrophotometrically studied. Kinetic analyses yielded the following information: MethB and MB were found to cause nonlinear inhibition of all recombinant BChEs except Y332A, compatible with a multi-site binding model. On the other hand, MethB and MB caused linear mixed inhibition of Y332A mutant, compatible with a single binding mode. Comparing the inhibitory effects in aspect of Ki values with recombinant wild type BChE (Ki=0.042 µM), MethB was found to be ∼30, 80 and 270-fold less effective as an inhibitor of Y332A, F329A and T120F, respectively. NB caused nonlinear inhibition of all recombinant BChEs. The inhibitory effect of NB on Y332A mutant was ∼370-fold lower, compared to recombinant wild type BChE (Ki=0.006 µM). Considering both kinetic and molecular docking results together, it was concluded that threonine 120, phenylalanine 329 and tyrosine 332 are critical amino acids in binding of cationic phenoxazine/phenothiazine structured ligands to human BChE.