Tau nuclear translocation is a leading step in tau pathology process through P53 stabilization and nucleolar dispersion.

Tau protein abnormalities are associated with various neurodegenerative disorders, including Alzheimer's disease (AD) and traumatic brain injury (TBI). In tau-overexpressing SHSY5Y cells and iPSC-derived neuron models of frontotemporal dementia (FTD), axonal tau translocates into the nuclear compartment, resulting in neuronal dysfunction. Despite extensive research, the mechanisms by which tau translocation results in neurodegeneration remain elusive thus far. We studied the nuclear displacement of different P-tau species [Cis phosphorylated Thr231-tau (cis P-tau), phosphorylated Ser202/Thr205-tau (AT8 P-tau), and phosphorylated Thr212/Ser214-tau (AT100 P-tau)] at various time points using starvation in primary cortical neurons and single severe TBI (ssTBI) in male mouse cerebral cortices as tauopathy models. While all P-tau species translocated into the somatodendritic compartment in response to stress, cis P-tau did so more rapidly than the other species. Notably, nuclear localization of P-tau was associated with p53 apoptotic stabilization and nucleolar stress, both of which resulted in neurodegeneration. In summary, our findings indicate that P-tau nuclear translocation results in p53-dependent apoptosis and nucleolar dispersion, which is consistent with neurodegeneration.

Role of cerebrospinal fluid in differentiation of human dental pulp stem cells into neuron-like cells.

Human dental pulp stem cells (hDPSCs) could be differentiated into neuron like-cells under particular microenvironments. It has been reported that a wide range of factors, presented in cerebrospinal fluid (CSF), playing part in neuronal differentiation during embryonic stages, we herein introduce a novel culture media complex to differentiate hDPSCs into neuron-like cells. The hDPSCs were initially isolated and characterized. The CSF was prepared from the Cisterna magna of 19-day-old Wistar rat embryos, embryonic cerebrospinal fluid (E-CSF). The hDPSCs were treated by 5% E-CSF for 2 days, then neurospheres were cultured in DMEM/F12 supplemented with 10-6 µm retinoic acid (RA), glial-derived neurotrophic factor and brain-derived neurotrophic factor for 6 days. The cells which were cultured in basic culture medium were considered as control group. Morphology of differentiated cells as well as process elongation were examined by an inverted microscope. In addition, the neural differentiation markers (Nestin and MAP2) were studied employing immunocytochemistry. Neuronal-like processes appeared 8 days after treatment. Neural progenitor marker (Nestin) and a mature neural marker (MAP2) were expressed in treated group. Moreover Nissl bodies were found in the cytoplasm of treated group. Taking these together, we have designed a simple protocol for generating neuron-like cells using CSF from the hDPSCs, applicable for cell therapy in several neurodegenerative disorders including Alzheimer's disease.

Immunohistochemical and Electron Microscopic Study of the Inhibitory Effects of Olive Oil Polyphenol on Dexamethasone-Induced Apoptosis.

BACKGROUND: There is accumulating evidence that a polyphenol present in olive oil, oleuropein, has antioxidant, anti-inflammatory and anti-apoptotic effects. This study aimed at determining the anti-apoptotic effect of Oleuropein (Ole) on dexamethasone-induced apoptosis of mouse thymocytes. METHOD: Mice were randomly divided to four groups as follow: Dexamethasone (Dex)-treated group (20 mg/kg; single dose), Ole-treated group (20 mg/kg per day), Dex plus Ole-treated group, and vehicle group. Sections of thymus were taken 16 hours after dexamethasone injection and studied for histopathological and immunohistochemistry assessment. RESULT: Further characteristics of degeneration in thymocytes were observed in the Dex group compared with the Dex plus Ole group. Compared with the Dex group (10.94±3.35), positive staining for Bax in thymocytes decreased in Dex plus Ole group (2.64±1.26), but remained higher than the Ole (0.65±0.30) and vehicle (0.67±0.29) groups. Compared with the Dex group (2.94±0.42), positive staining for Bcl-2 in thymocytes increased in Dex plus Ole group (12.24±1.84) yet was lower than the Ole (14.94±1.54) and vehicle (18.93±3.54) groups. CONCLUSION: Our results suggest that dexamethasone-induced apoptosis is subsided by oleuropein.