ABSTRACT
Niemann-Pick disease type C (NPC) is a fatal,neurovisceral lipid storage disease,neuropathologically characterized by cytoplasmic sequestration of glycolipids in neurons,progressive neuronal loss,neurofibrillary tangles (NFTs) formation,and axonal spheroids (AS).Cytoskeletal pathology including accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological hallmark of the mouse model of NPC (npc mice).With a goal of elucidating the mechanisms underlying the lesion formation,we investigated the temporal and spatial characteristics of cytoskeletal lesions and the roles of cdc2,cdk4,and cdk5 in lesion formation in young npc mice.Cytoskeletal lesions were detectable in npc mice at three weeks of age.Importantly,concomitant activation of cdc2/cyclin B 1 kinase and accumulation of a subsequently generated cohort of phospho-epitopes were detected.The activation of cdk4/cyclin D1 and cdk5/p25 kinases was observed during the fourth week of life in npc mice,and this activation contributed to the lesion formation.We concluded that the progression of cytoskeletal pathology in npc mice older than four weeks is accelerated by the cumulative effect of cdc2,cdk4,and cdk5 activation.Furthermore,cdc2/cyclin B1 may act as a key initial player one week earlier.Targeting cell cycle activation may be beneficial to slow down the NPC pathogenesis.
ABSTRACT
The aim of our study was to observe the occurrence rate and morphological characteristics of Infra-Lamina ridge (ILR) in Chinese population and provide a comprehensive reference for its clinical implication. Vertebrae columns of 82 sets of Chinese adult skeletons were collected. The shape of ILR was classified into three types; the occurrence of it in different sides and sexes were counted. The length, width, thickness of ILR were measured using a caliper with 0.02 mm accuracy. The ILR was usually found to occur from C7 to L5, with its frequency higher from T8 to 12, and highest at T10being up to 80.5%. There was significant statistical difference to the occurrence rate by side, sex and vertebral level. The largest values in its length and width were from T9 to T12. The ILR at T10 was largest in dimensions, being 4.1±2.1 mm in length and 4.4±2.3 mm in width. The ILR is more frequently detected in female and at the left side, at the lower thoracic spine with a larger dimension.
El objetivo de nuestro estudio fue observar la tasa de incidencia y características morfológicas del puente infra-laminar (PIL) en la población china y ofrecer una referencia completa por su implicación clínica. Se utilizaron 82 series de vértebras pertenecientes a esqueletos adultos chinos. La forma del PIL se clasificó en tres tipos; además se cuantificó la presenciade la misma en diferentes lados y sexos. La longitud, ancho y grosor del PIL se midieron utilizando un caliper con 0,02 mm de precisión. Se encontró que el PIL por lo general se producía desde C7 a L5 , con una mayor frecuencia entre T8 y T12, la más alta en T10 donde alcanzó el 80,5%. No hubo diferencia estadísticamente significativa en la tasa de ocurrencia según lado, sexo y el nivel de la vértebra. Los mayores valores de longitud y ancho fueron de T9 a T12. El PIL en T10 tuvo las mayores dimensiones, con una longitud de 4,1±2,1 mm y ancho de 4,4±2,3 mm. El PIL se detecta con mayor frecuencia en mujeres y la lado izquierdo, con una mayor dimensión en la columna torácica inferior.