Ultrastructural study of the hypothalamus in mice chronically treated with manganese / Estudio ultraestructural del hipotálamo de ratones tratados crónicamente con manganeso

Manganese (Mn) is an essential metal that is an integral part of some metalloproteins and acts as a cofactor of several enzymes. Mn is able to cross the blood-brain barrier and enter the nervous system. It has a low toxicity but exposure to high concentrations or for prolonged periods of time produce neurological disorders in humans that initially cause hallucinations and compulsive behaviour followed by stiffness, muscle weakness, ataxia, memory loss and a tremor resembling Parkinson’s disease. This study assessed the ultrastructural alterations produced in the hypothalamus of male albino mice injected intraperitoneally with MnCl2 (5 mg Mn/Kg/day) and a control group injected with NaCl 0.9% (0.1 mL) daily for 9 weeks. The animals were sacrificed by cervical dislocation. The hypothalamus was extracted and subsequently processed to be observed on the conventional transmission electron microscope at 2, 4, 6 and 9 weeks of treatment. After 2 weeks it was observed a slight disruption of the Golgi apparatus and the myelin fibers. After 4 weeks the disorganization was accentuated and dilatation of the endoplasmic reticulum (ER) and alterations of mitochondria were observed. After 6 weeks the normal pattern of the myelin sheath was lost. After 9 weeks of treatment it was found swollen mitochondria with lost of crystae, a marked dilatation of rough and smooth endoplasmic reticulum and dendrites with a high degree of swelling. These results suggest that the neurotoxic effect of Mn increases as time of exposure passes and produces ultrastructural alterations of nerve cells in the hypothalamus.

El manganeso (Mn) es un metal esencial que forma parte de algunas metaloproteínas y actúa como cofactor de varias enzimas. El Mn es capaz de atravesar la barrera hematoencefálica e ingresar al sistema nervioso. Presenta baja toxicidad, pero la exposición a altas concentraciones o por tiempos prolongados produce alteraciones neurológicas en humanos que inicialmente provocan alucinaciones y conducta compulsiva seguidas por rigidez, debilidad muscular, ataxia, pérdida de la memoria y temblor, síntomas similares a los de la enfermedad de Parkinson. En el presente estudio se evaluaron los efectos tóxicos del Mn sobre la ultraestructura del hipotálamo de ratones. Se inyectaron intraperitonealmente ratones albinos machos con MnCl2 (5 mg Mn/Kg/día durante 9 semanas). El grupo control recibió NaCl 0,9% (0,1 mL/dosis). Los animales se sacrificaron por dislocación cervical, extrayéndose y disecándose el hipotálamo, que posteriormente se procesó para realizar observaciones al microscopio electrónico de transmisión convencional a las 2; 4; 6 y 9 semanas de tratamiento. A las 2 semanas, se observó ligera desorganización en el aparato de Golgi y en las fibras mielínicas. A las 4 semanas, se acentuó la desorganización y se comenzó a observar dilatación del retículo endoplasmático liso y rugoso asi como mitocondrias alteradas. A las 6 semanas, se encontró pérdida del patrón normal de la cubierta mielínica. Finalizadas las 9 semanas de tratamiento, se observaron mitocondrias hinchadas con pérdida de las crestas, dilatación acentuada del retículo endoplasmático rugoso y liso y dendritas con cierto grado de edema. Estos resultados parecen indicar que el efecto neurotóxico del Mn aumenta a medida que transcurre el tiempo de exposición para producir alteraciones ultraestructurales de las células nerviosas del hipotálamo.

Ultrastructural changes of the olfactory bulb in manganese-treated mice

The effect of manganese toxicity on the ultrastructure of the olfactory bulb was evaluated. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/Kg/day) five days per week during nine weeks. The control group received NaCl (0.9%). The olfactory bulbs of five mice from each group were processed for transmission electron microscopy after 2, 4, 6 and 9 weeks of manganese treatment. On week 2, some disorganization of the myelin sheaths was observed. After 4 weeks, degenerated neurons with dilated cisternae of rough endoplasmic reticulum and swollen mitochondria appeared. A certain degree of gliosis with a predominance of astrocytes with swollen mitochondria, disorganization of the endomembrane system, dilation of the perinuclear cisternae and irregularly shaped nuclei with abnormal chromatin distribution were observed after 6 weeks. Some glial cells showed disorganization of the Golgi apparatus. On week 9, an increase in the number of astrocytes, whose mitochondrial cristae were partially or totally erased, and a dilation of the rough endoplasmic reticulum were found. Neurons appear degenerated, with swollen mitochondria and a vacuolated, electron dense cytoplasm. These changes seem to indicate that the olfactory bulb is sensitive to the toxic effects of manganese.(AU)

Ultrastructural changes of the olfactory bulb in manganese-treated mice

The effect of manganese toxicity on the ultrastructure of the olfactory bulb was evaluated. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/Kg/day) five days per week during nine weeks. The control group received NaCl (0.9%). The olfactory bulbs of five mice from each group were processed for transmission electron microscopy after 2, 4, 6 and 9 weeks of manganese treatment. On week 2, some disorganization of the myelin sheaths was observed. After 4 weeks, degenerated neurons with dilated cisternae of rough endoplasmic reticulum and swollen mitochondria appeared. A certain degree of gliosis with a predominance of astrocytes with swollen mitochondria, disorganization of the endomembrane system, dilation of the perinuclear cisternae and irregularly shaped nuclei with abnormal chromatin distribution were observed after 6 weeks. Some glial cells showed disorganization of the Golgi apparatus. On week 9, an increase in the number of astrocytes, whose mitochondrial cristae were partially or totally erased, and a dilation of the rough endoplasmic reticulum were found. Neurons appear degenerated, with swollen mitochondria and a vacuolated, electron dense cytoplasm. These changes seem to indicate that the olfactory bulb is sensitive to the toxic effects of manganese.

Ultrastructural changes of the olfactory bulb in manganese-treated mice.

The effect of manganese toxicity on the ultrastructure of the olfactory bulb was evaluated. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/Kg/day) five days per week during nine weeks. The control group received NaCl (0.9%). The olfactory bulbs of five mice from each group were processed for transmission electron microscopy after 2, 4, 6 and 9 weeks of manganese treatment. On week 2, some disorganization of the myelin sheaths was observed. After 4 weeks, degenerated neurons with dilated cisternae of rough endoplasmic reticulum and swollen mitochondria appeared. A certain degree of gliosis with a predominance of astrocytes with swollen mitochondria, disorganization of the endomembrane system, dilation of the perinuclear cisternae and irregularly shaped nuclei with abnormal chromatin distribution were observed after 6 weeks. Some glial cells showed disorganization of the Golgi apparatus. On week 9, an increase in the number of astrocytes, whose mitochondrial cristae were partially or totally erased, and a dilation of the rough endoplasmic reticulum were found. Neurons appear degenerated, with swollen mitochondria and a vacuolated, electron dense cytoplasm. These changes seem to indicate that the olfactory bulb is sensitive to the toxic effects of manganese.

Tumoral micro-blood vessels and vascular microenvironment in human astrocytic tumors. A transmission electron microscopy study.

The development of peritumoral edema is thought to be due to extravasation of plasma water and macromolecules through a defective blood-brain barrier (BBB), but the exact mechanism by which occurs is poorly understood. The aim of this study was analyze at submicroscopic level the morphological changes in both micro-blood vessels and vascular microenvironment of astrocytic tumors in an attempt of understanding the pathological aspects that may help in the future researches for the design of future therapeutic strategies. Biopsies of 25 patients with pathological diagnosis of astrocytic tumors were examined with the transmission electron microscope. Both open and close tight junctions were observed in the micro-blood vessels, inclusive in a same tumor. Cytoskeletal disorganization associated with disintegrated perijunctional actin filaments were seen. The paracellular space showed enlargement and commonly occupied by fluid proteinaceous, endothelial cells display oncotic and ischemic changes, basal lamina reveals enlargement, edema, vacuolization and collagen fibers disposed in irregular array. Pericytes exhibited edema and phagocytoced material, astrocytic perivascular-feet showed signs of oncosis and necrosis, co-option vessels totally surrounding by neoplastic cells also were seen. The ultrastructural abnormalities observed in both junctional complexes and vascular microenvironment suggest a multi-factorial pathobiology process, probably hypoxia intratumoral, calcium overload in endothelial cells, and degradative effects of metalloproteinases over the basal membrane appear as determinant factors that leading to structural modifications of junctional complexes, therefore, treatment with both HIF-1alpha and metalloproteinases inhibitors possibly can contribute with the pharmacological handling of the peritumoral edema associated with astrocytic tumors.

Glycogen-rich and glycogen-depleted astrocytes in the oedematous human cerebral cortex associated with brain trauma, tumours and congenital malformations: an electron microscopy study.

PRIMARY OBJECTIVE: The anaerobic mobilization of astrocyte glycogen in anoxic-ischemic regions of the oedematous human cerebral cortex is analysed. METHODS AND PROCEDURES: Seventeen cortical biopsies of patients with brain trauma, brain tumours and congenital malformations were examined by conventional transmission electron microscopy. RESULTS: Glycogen-rich and glycogen-depleted, clear or dense astrocytes cell bodies were observed in anoxic ischaemic regions of different brain cortical areas in perineuronal, neuropilar and perivascular localization. Glycogen-rich astrocytes showed clear or moderately dense cytoplasm and accumulation of both beta-type or monogranular glycogen granules and alpha-type or multigranular glycogen particles. Focal regions of translucent cytoplasm were observed in areas of glycogen degradation. Glycogen-depleted astrocytes exhibited a clear cytoplasm and scarce amount or absence of beta-type glycogen granules. Coexisting glycogen-rich and glycogen-depleted neuropilar astrocytic processes were observed in the vicinity of degenerated myelinated axons and degenerated axodendritic contacts. Glycogen-rich and glycogen-depleted perivascular astrocytic processes were also found surrounding injured and collapsed cerebral capillaries. CONCLUSION: The findings suggest astrocytic glycogen mobilization during anoxic and ischaemic conditions, revealing the important contribution of astrocytes on neuronal survival under conditions of energy substrate limitations.

Interleucina-10 y quimioprevención retinoide del cáncer de mama experimental / Interleukina-10 and retinoid chemoprevention in experimental breast cancer

Estudiar las concentraciones de interleucina-10 en el suero de ratas tratadas con 7-13 dimetil-benzantraceno, ácido retinoico y una combinación de ambos. Cátedra de Inmunología, Instituto de Investigaciones Biológicas y Facultad de Veterinaria. Universidad del Zulia. Investigación longitudinal, antes y después de recibir las sustancias experimentales. La citocina se cuantificó por inmunoanálisis enzimatico (ELISA) de doble anticuerpo. Incremento de la citocina sérica en animales que recibieron la combinación (grupo A) y en los que recibieron el cancerígeno solo (grupo B), pero más significativo en los primeros. En el grupo A no se observaron tumores, pero sí en el B. El retinoide solo (grupo C) también indujo un ascenso, precoz y significativo, con el desenso posterior a la normalidad, cuando aún permanecían valores elevados en los grupos A y B. No se formaron tumores en los animales del grupo C. Las dos sustancias estudiadas producen aisladamente aumento en la secreción de la citocina. Las cantidades mayores de interleucina-10, dadas sus características biológicas, parecen producir cambios en la evolución tumoral.