Decreased phosphatidylethanolamine binding protein expression correlates with Aβ accumulation in the Tg2576 mouse model of Alzheimer's disease

Phosphatidylethanolamine binding protein (PEBP) is a multifunctional protein, with proposed roles as the precursor protein of hippocampal cholinergic neurostimulating peptide (HCNP), and as the Raf kinase inhibitor protein (RKIP). Previous studies have demonstrated a decrease in PEBP mRNA in CA1 region of AD hippocampus. The current study demonstrates that PEBP is decreased in the hippocampus of 11 month Tg2576 mice, in the absence of change in mRNA levels compared to non-transgenic littermates. The level of PEBP in transgenic mouse hippocampus significantly decreases at 11 months (a time point when Aβ begins accumulating) and 15 months (when Aβ plaques have formed). There was a significant correlation between decreased PEBP expression and accumulation of Aβ. Immunohistochemical studies on Tg2576 and AD brain sections demonstrate that PEBP immunoreactivities are present at the periphery of dense multicore Aβ plaques, and in selective astrocytes, primarily surrounding plaques. These findings suggest that PEBP expression may be influenced by accumulation of Aβ. Down-regulation of PEBP may result in lower levels of HCNP or altered coordination of signal transduction pathways that may contribute to neuronal dysfunction and pathogenesis in AD

Biomedical studies on temporal bones of the first multi-channel cochlear implant patient at the University of Melbourne

Objective: To analyse the temporal bones and implant of the first University of Melbourne’s (UOM) patient (MC-1) to receive the multi-channel cochlear prosthesis.Methods: The left cochlea was implanted with the prototype multi-channel cochlear prosthesis on 1 August 1978, and the Cochlear versions CI-22 and CI-24 on 22 June 1983 and 10 November 1998, respectively. MC-1 died in 2007.Results: Plain X-rays of the temporal bones showed that after the CI-22 had been explanted seven electrode bands remained in situ. Micro-CT scans also revealed a partially united fracture transecting the left implanted and right control cochleae. Histology indicated a total loss of the organ of Corti on both sides, and a tear of the left basilar membrane. In addition, there was a dense fibrous capsule with heterotopic bone surrounding one proximal band of the CI-22 array that restricted its removal. This pathology was associated with dark particulate material within macrophages, probably due to the release of platinum from the electrode bands. Scanning electron microscopy (SEM) showed possible corrosion of platinum and surface roughening. Three-dimensional reconstruction of the cochlear histology demonstrated the position of the electrode tracts (C1-22 and CI-24) in relation to the spiral ganglion, which showed 85–90% loss of ganglion cells.Discussion and conclusions: This study confirms our first histopathological findings that our first free-fitting banded electrode array produced moderate trauma to the cochlea when inserted around the scala tympani of the basal turn. The difficulty in extraction was most likely due to one band being surrounded by an unusually large amount of fibrous tissue and bone, with an electrode band caught due to surface irregularities. Some surface corrosion and a small degree of platinum deposition in the tissue may also help explain the outcome for this long-term cochlear implantation.</p

Biomedical studies on temporal bones of the first multi-channel cochlear implant patient at the University of Melbourne

Objective: To analyse the temporal bones and implant of the first University of Melbourne’s (UOM) patient (MC-1) to receive the multi-channel cochlear prosthesis.Methods: The left cochlea was implanted with the prototype multi-channel cochlear prosthesis on 1 August 1978, and the Cochlear versions CI-22 and CI-24 on 22 June 1983 and 10 November 1998, respectively. MC-1 died in 2007.Results: Plain X-rays of the temporal bones showed that after the CI-22 had been explanted seven electrode bands remained in situ. Micro-CT scans also revealed a partially united fracture transecting the left implanted and right control cochleae. Histology indicated a total loss of the organ of Corti on both sides, and a tear of the left basilar membrane. In addition, there was a dense fibrous capsule with heterotopic bone surrounding one proximal band of the CI-22 array that restricted its removal. This pathology was associated with dark particulate material within macrophages, probably due to the release of platinum from the electrode bands. Scanning electron microscopy (SEM) showed possible corrosion of platinum and surface roughening. Three-dimensional reconstruction of the cochlear histology demonstrated the position of the electrode tracts (C1-22 and CI-24) in relation to the spiral ganglion, which showed 85–90% loss of ganglion cells.Discussion and conclusions: This study confirms our first histopathological findings that our first free-fitting banded electrode array produced moderate trauma to the cochlea when inserted around the scala tympani of the basal turn. The difficulty in extraction was most likely due to one band being surrounded by an unusually large amount of fibrous tissue and bone, with an electrode band caught due to surface irregularities. Some surface corrosion and a small degree of platinum deposition in the tissue may also help explain the outcome for this long-term cochlear implantation.</p