Anti-aging effect of simvastatin on retinas of rats and its potential mechanisms / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To investigate the anti - aging effect and its potential mechanisms of simvastatin on retinas of physiological aging rats.·METHODS:Totally 40 three-month old healthy SD rats which had no eye diseases, were randomly assigned into two groups: simvastatin group ( n = 20 ) and control group ( n=20 ) . All rats were cultivated under the same conditions until they were nine - month old when interventions started to be given. Simvastatin group was given intragastric administration of 5mg/kg simvastatin every day until 17-month old. Control group was given intragastric administration of same amount of saline gavage. Retinal thickness was measured by HE staining, while Cu - Zn - SOD, NOX2, Bcl - 2 and Bax were determined by immunohistochemistry ( IHC) .·RESULTS:HE staining showed that the retinal structure was clearer; the morphology of cell was more homogeneous;the number of cells was more stable and the structure of retinal pigment epithelium was more compact when compared with control group. Thickness of retinal neuroepithelium layer and retinal pigment epithelium increased significantly in the simvastatin group. Immunohistochemistry analysis showed that the expressions of Cu - Zn - SOD and Bax statistically increased while the NOX2, Bcl-2 as well as Bcl-2/Bax decreased in simvastatin group when compared with control group (P<0. 05).·CONCLUSION: Simvastatin plays a protective role in retinal aging by decreasing oxidative stress reaction and promoting cell apoptosis.

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma

BACKGROUND: Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT. METHODS: The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases. RESULTS: CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001). CONCLUSIONS: Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.

La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias / Melatonin as a neuronal differentiation factor: therapeutic implications for dementia

Dementias are progressive and neurodegenerative neuropsychiatry disorders, with a high worldwide prevalence. These disorders affect memory and behavior, causing impairment in the performance of daily activities and general disability in the elders. Cognitive impairment in these patients is related to anatomical and structural alterations at cellular and sub-cellular levels in the Central Nervous System. In particular, amyloid plaques and neurofibrillar tangles have been defined as histopathological hallmarks of Alzheimer's disease. Likewise, oxidative stress and neuroinflammation are implicated in the etiology and progression of the disease. Neuronal precursors from human olfactory neuroepithelium have been recently characterized as an experimental model to identify neuropsychiatric disease biomarkers. Moreover, this model not only allows the study of neuropsychiatric physiopathology, but also the process of neurodevelopment at cellular, molecular and pharmacological levels. This review gathers the evidence to support the potential therapeutic use of melatonin for dementias, based on its antioxidant properties, its anti-inflammatory effect in the brain, and its ability to inhibit both tau hyper-phosphorylation and amyloid plaque formation. Furthermore, since melatonin stimulates neurogenesis, and promotes neuronal differentiation by inducing the early stages of neuritogenesis and dendrite formation, it has been suggested that melatonin could be useful to counteract the cognitive impairment in dementia patients.

Las demencias son enfermedades neuropsiquiátricas, progresivas, neurodegenerativas y con una alta prevalencia a nivel mundial. Ocupan uno de los primeros lugares como enfermedades que causan incapacidad en los adultos mayores. En estos pacientes el Sistema Nervioso Central presenta alteraciones anatómico-estructurales a nivel celular y subcelular que se asocian con deficiencias cognitivas. En particular, en la enfermedad de Alzheimer se han caracterizado marcadores histopatológicos como las placas amiloides y las marañas neurofibrilares. Se sabe que el estrés oxidativo y la neuroinflamación participan en la etiología y el desarrollo de la enfermedad. Recientemente se caracterizó a los precursores neuronales del neuroepitelio olfatorio humano como un modelo experimental adecuado para identificar biomarcadores de rasgo y para estudiar la fisiopatología de diversas enfermedades neuropsiquiátricas, así como el proceso del neurodesarrollo, a nivel celular, molecular y farmacológico. En este trabajo se presenta la evidencia que sustenta que la melatonina puede ser útil en el tratamiento de las demencias, por su capacidad antioxidante, por su efecto anti-inflamatorio, así como por el efecto inhibidor de la hiperfosforilación de la proteina tau y de la formación de placas amiloides. Además, al estimular la formación de nuevas neuronas, la neuritogénesis en sus etapas tempranas y la formación de dendritas, la melatonina podría contribuir a contrarrestar la pérdida de las funciones cognitivas que se observa en estos padecimientos.

Immature teratoma of the ovary: A clinicopathological study of 28 cases.

Aim: Immature teratoma (IT) of the ovary represents 1% of all ovarian cancers and 20% of malignant ovarian germ cell tumors. This retrospective study of 28 such cases aims to look at its morphological spectrum and to study the correlation of the grade and stage of the tumor with prognosis. Materials and Methods: A retrospective study of 28 cases of IT of the ovary was done. Neuroepithelium was graded as grade I, II and III according to the standard criteria. The presence of immature mesenchyme was also looked for and similarly graded. Results: The median age for the cases was 19 years and abdominal pain was the commonest symptom. Neuroepithelium was seen in 26 cases (6 were grade I, 13 were grade II, and 7 were grade III); and two showed immature mesenchymal tissue (IM) only. IM was seen in all 28 cases, but no correlation with the grade of the IT of the ovary is found. The follow up is available in 23 cases ranging from 6 months to 78 months (median 33 months). Of these, 13 were stage I, 3 were stage II and 7 were stage III ITs. Out of 23 patients, 17 patients were alive without evidence of disease recurrence during the last follow up. Adverse events in the form of death and local recurrence occurred in 6 patients. One patient died of the disease at 7 months duration from the disease onset (stage III, grade II IT). Conclusion: Morphological spectrum of IT of ovary is varied. Immature mesenchyme was seen in all the cases of IT of ovary and its presence should prompt a careful search for immature neuroepithelium. Stage I IT of ovary has better prognosis. Combination of surgery and chemotherapy can give longer survival even in recurrent disease.

Changes in the Histone Acetylation Patterns during the Development of the Nervous System

Epigenetic modification such as DNA methylation and histone acetylation plays essential roles in many aspects of cellular function and development of animals. There is an increasing amounts of evidence for dynamic changes in the histone acetylation of specific gene segments, but little attempt was made to examine global pattern changes in the histone acetylation in developing nervous system. In this study, we found that acetylated histone H3 and H4 immunoreactivities were relatively weak in neuroepithelial cells in the ventricular zone of developing rat cerebral cortex or chick spinal cord, compared to the immature young neurons in the cortical plate of a rat embryo or lateral motor column in chick spinal cord. On the other hand, adult neural stem cells in the dentate gyrus (DG) of rat hippocampal formation did not exhibit such diminished histone acetylation, compared to neuroblasts and mature DG neurons. These results suggest that the level of histone acetylation is highly dynamic and tightly linked to the neuronal types and the differentiation stages.

The Impact of Toxicants on the Olfactory System

The olfactory system is valuable in the study of some general properties of neural system and it provides as an excellent model for studying the effects of environmental toxicants on the sensory system. For example, the olfactory receptor neuron has become an important neurobiologic model system in the area of molecular and cell biology for the study of neuronal plasticity and neuronal development, including the developmental steps of cell birth and lineage, differentiation, synaptogenesis, migration, maturation, and death. The olfactory neuroepithelium is characteristic of neuron replacement and regeneration throughout life. Olfactory receptor neurons are rapidly replaced following traumatic lesions and they are the only known projection neurons with this property. Various toxicants put the olfactory system at risk for damage. Toxic agents comprise part of health hazard to human olfaction. However, the direct and indirect effects of these agents on the olfactory system are not completely understood.

ISOLATION AND INDUCED DIFFERENTIATION OF NEUROEPITHELIAL STEM CELLS FROM SPINAL CORD NEURAL TUBE / 解剖学报

Objective To isolate neuroepithelial stem cells from the spinal cord neural tube of the embryonic rat and induce them to differentiate into dopaminergic neurons. Methods Serum free cells suspension culture and single cell cloning technique were used to isolate neuroepithelial stem cells. 5 bromo 2 deoxyuridine(BrdU) to label new cells combined with single or double immunocytochemistry staining to detect nestin antigen before differentiation and neural cell specific antigens after differentiation, such as neurofilament (NFM 160?kD), glial fibrillary acidic protein(GFAP), galactocerebroside(GalC) and tyrosine hydroxylase(TH). Striatal extracts were used to induce neuroepithelial stem cells to differentiate into dopaminergic neurons. Results The cells isolated from the spinal cord neural tube of the embryonic rat expressed nestin antigen. They had the potential to serially passage and differentiate into neurons, astrocytes and oligodendrocytes. Striatal extracts could induce 12% of them to differentiate into dopaminergic neurons compared with 3% in controls.Conclusion The cells, which express nestin antigen, isolated from neural tube are multipotent and have the ability to self renew, therefore, they are neural stem cells. These stem cells can be induced to differentiate into specific neurons in vitro. Which can provide materials for neural transplantation.