RESUMEN
Amyloid deposition in Alzheimer fibrils forms neurotoxic senile plaques in a process that may be modulated by associated proteins. In this work we demonstrate the ability of laminin-1 and laminin-2 to inhibit fibril formation and toxicity on cultured rat hippocampal neurons. We confirm that the laminin-1-derived peptide YFQRYLI inhibits efficiently both fibril formation and neurotoxicity and show that the IKVAV peptide inhibits amyloid neurotoxicity despite its slight inhibition of fibril formation. On other hand, laminin-1 induces disaggregation of preformed fibrils in vitro, characterized as a progressive disassembly of fibrils into protofibrils and further clearance of these latter species, leading to a continual inhibition of amyloid neurotoxicity.
Asunto(s)
Péptidos beta-Amiloides/toxicidad , Laminina/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/toxicidad , Polímeros/metabolismo , Péptidos beta-Amiloides/ultraestructura , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Hipocampo/citología , Humanos , Cinética , Ratones , Neurofibrillas/ultraestructura , Neuronas/citología , Neurotoxinas/antagonistas & inhibidores , Fragmentos de Péptidos/química , Fragmentos de Péptidos/ultraestructura , RatasRESUMEN
Human T-cell lymphotropic virus type I (HTLV-I), is the cause of endemic tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). Because TSP/HAM is not a fatal disease, the neuropathology of this disease, albeit relatively well understood, is based on the examination of just a few incidental cases. Previously, we demonstrated peculiar lamellated structures, called "multilamellar bodies" (MLB). In this report, we present the ultrastructural neuropathology of a TSP/HAM case from Chile, with further detailed descriptions of MLB. It is tempting to suggest that MLB may represent specific ultrastructural markers of TSP/HAM. The pathology of the anterior and posterior horns was similar and was comprised of axonal degeneration, accompanied by extensive astrocytic gliosis. Lymphocytic infiltration, particularly observed as "cuffs" around blood vessels, was scattered among other cellular elements. Ultrastructurally, myelin sheaths were relatively well preserved, and some demyelinated but not remyelinated fibers were observed. Moreover, axons with abnormal accumulations of neurofilaments, suggestive of axonal degeneration, were detected. Several axons contained Hirano bodies. In many samples, glial processes replaced most of the remaining neuropil. In a few specimens of the anterior and posterior horns of the spinal cord, MLB were observed. These structures consisted of stacks of 30 to 40 electron-dense lamellae, which were interrupted by narrow electron-lucent spaces. All of the lamellae were immersed within an amorphous substance of intermediate density. Neurons of the dorsal root ganglia were basically normal except for increased lipofuscin accumulation. As in the spinal cord, myelinated axons were well preserved, but a few were demyelinated and surrounded by concentric arrays of Schwann cell membranes. Also, axons of the dorsal roots accumulated increased number of neurofilaments. Mast cells and Schwann cells were increased in number, the latter containing abundant pi granules and myelin fragments.
Asunto(s)
Lóbulo Frontal/ultraestructura , Ganglios Espinales/ultraestructura , Músculo Esquelético/ultraestructura , Paraparesia Espástica Tropical/patología , Médula Espinal/ultraestructura , Astrocitos/ultraestructura , Axones/ultraestructura , Chile , Glucógeno/metabolismo , Humanos , Lipofuscina/metabolismo , Linfocitos/patología , Vaina de Mielina/ultraestructura , Miofibrillas/ultraestructura , Neurofibrillas/ultraestructura , Vacuolas/ultraestructuraRESUMEN
Acetylcholinesterase (AChE), an important component of cholinergic synapses, colocalizes with amyloid-beta peptide (A beta) deposits of Alzheimer's brain. We report here that bovine brain AChE, as well as the human and mouse recombinant enzyme, accelerates amyloid formation from wild-type A beta and a mutant A beta peptide, which alone produces few amyloid-like fibrils. The action of AChE was independent of the subunit array of the enzyme, was not affected by edrophonium, an active site inhibitor, but it was affected by propidium, a peripheral anionic binding site ligand. Butyrylcholinesterase, an enzyme that lacks the peripheral site, did not affect amyloid formation. Furthermore, AChE is a potent amyloid-promoting factor when compared with other A beta-associated proteins. Thus, in addition to its role in cholinergic synapses, AChE may function by accelerating A beta formation and could play a role during amyloid deposition in Alzheimer's brain.
Asunto(s)
Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/enzimología , Péptidos beta-Amiloides/metabolismo , Encéfalo/enzimología , Neurofibrillas/metabolismo , Amiloide/metabolismo , Péptidos beta-Amiloides/genética , Animales , Benzotiazoles , Sitios de Unión , Encéfalo/ultraestructura , Butirilcolinesterasa/metabolismo , Bovinos , Colorantes Fluorescentes , Humanos , Ratones , Microscopía Electrónica , Mutación , Neurofibrillas/ultraestructura , Propidio/farmacología , Proteínas Recombinantes/metabolismo , Espectrometría de Fluorescencia , Tiazoles/metabolismoRESUMEN
The projection from the retina to the dorsal lateral geniculate nucleus in the primate arises from two morphologically distinct types of ganglion cells. The P-ganglion cells project to the parvocellular layers, the M-ganglion cells to the magnocellular layers. We have developed a neurofibrillar stain which stains the M-ganglion cell population with a high degree of selectivity allowing us to map their distribution across the retina. As with other ganglion cell types the M-ganglion cell density peaks close to the fovea and declines towards the periphery. At 1 mm from the fovea the proportion of M-ganglion cells ranges from 6 to 10% and then increases to about 8-10% over much of the retina except along the nasal horizontal meridian. Along the nasal horizontal meridian the percentage increases from 10% at 7 mm eccentricity to 20% or more at higher eccentricities. The increased percentage of M-ganglion cells in the nasal quadrant of the retina correlates with the relatively smaller dendritic trees of M-ganglion cells in this region.
Asunto(s)
Cuerpos Geniculados/fisiología , Macaca/fisiología , Células Ganglionares de la Retina/fisiología , Transmisión Sináptica , Animales , Recuento de Células , Peroxidasa de Rábano Silvestre , Macaca fascicularis , Macaca mulatta , Neurofibrillas/ultraestructura , Retina/citología , Retina/ultraestructura , Células Ganglionares de la Retina/citología , Coloración y EtiquetadoRESUMEN
A simple modification of a reduced silver-stain for neurofilaments is described. Using neutral pH, perfusion fixation, and heat treatment during postfixation this method greatly improves the quality and reliability of staining of ganglion cells in retinal wholemounts from primate and other species. In addition it permits the selective staining of some cell populations thought to be refractory to silver stains. The method also stains cutaneous receptors in thick sections of the glabrous skin.
Asunto(s)
Neurofibrillas/ultraestructura , Retina/ultraestructura , Piel/inervación , Coloración y Etiquetado/métodos , Animales , Cebus , Fijadores , Formaldehído , Macaca , Reproducibilidad de los Resultados , Células Ganglionares de la Retina/ultraestructura , Coloración y Etiquetado/normasRESUMEN
The authors present a study on ultrastructural changes observed in aged human and animal brain. These changes are analyzed and compared with those described in classic optic microscopy and with those observed in experimental models of the same lesions.