“
“Pretangles are cytoplasmic tau immunoreactivity in neurons without apparent formation of fibrillary structures. In Alzheimer disease, such tau deposition is considered to represent a premature state prior to fibril formation (AD-pretangles), later to form neurofibrillary

BMS 354825 tangles and finally ghost tangles. This morphological evolution from pretangles to ghost tangles is in parallel with their profile shift from four repeat (4R) tau-positive pretangles to three repeat (3R) tau-positive ghost tangles with both positive neurofibrillary tangles in between. This complementary shift of tau profile from 4R to 3R suggests that these tau epitopes are represented interchangeably along tangle evolution. Similar tau immunoreactivity without fibril formation is also observed in corticobasal degeneration (CBD-pretangles). CBD-pretangles and AD-pretangles share: (i) selective 4R tau immunoreactivity without involvement of 3R tau; and (ii) argyrophilia with Gallyas silver impregnation. However, CBD-pretangles neither evolve into ghost tangles nor exhibit 3R tau

immunoreactivity even at the advanced stage. Because electron microscopic studies on these pretangles are selleckchem quite limited, it remains to be clarified whether such differences in later evolution are related to their primary ultrastructures, potentially distinct Rebamipide between AD and CBD. As double staining for 3R and 4R tau clarified complementary shift from 4R to 3R tau along evolution from pretangles to ghost tangles, double immunoelectron microscopy, if possible, may

clarify similar profile shifts in relation to each tau fibril at the ultrastructural dimension. This will provide a unique viewpoint on how molecular (epitope) representations are related to pathogenesis of fibrillary components. “
“This chapter contains sections titled: Introduction Anatomy and Physiology of the Innerear Access of Ototoxicants to the Inner Ear Methods for Studying the Inner Ear Effects and Actions of Ototoxic Drugs Classes of Ototoxic Agents Ototoxic Interactions Summary References “
“Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of DNAX-activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). TREM2 and DAP12 constitute a receptor/adapter signaling complex expressed on osteoclasts, dendritic cells (DC), macrophages and microglia. Previous studies using knockout mice and mouse brain cell cultures suggest that a loss-of-function of DAP12/TREM2 in microglia plays a central role in the neuropathological manifestation of NHD. However, there exist no immunohistochemical studies that focus attention on microglia in NHD brains.