32 research outputs found

    RBM3 mediates structural plasticity and protective effects of cooling in neurodegeneration.

    Get PDF
    In the healthy adult brain synapses are continuously remodelled through a process of elimination and formation known as structural plasticity. Reduction in synapse number is a consistent early feature of neurodegenerative diseases, suggesting deficient compensatory mechanisms. Although much is known about toxic processes leading to synaptic dysfunction and loss in these disorders, how synaptic regeneration is affected is unknown. In hibernating mammals, cooling induces loss of synaptic contacts, which are reformed on rewarming, a form of structural plasticity. We have found that similar changes occur in artificially cooled laboratory rodents. Cooling and hibernation also induce a number of cold-shock proteins in the brain, including the RNA binding protein, RBM3 (ref. 6). The relationship of such proteins to structural plasticity is unknown. Here we show that synapse regeneration is impaired in mouse models of neurodegenerative disease, in association with the failure to induce RBM3. In both prion-infected and 5XFAD (Alzheimer-type) mice, the capacity to regenerate synapses after cooling declined in parallel with the loss of induction of RBM3. Enhanced expression of RBM3 in the hippocampus prevented this deficit and restored the capacity for synapse reassembly after cooling. RBM3 overexpression, achieved either by boosting endogenous levels through hypothermia before the loss of the RBM3 response or by lentiviral delivery, resulted in sustained synaptic protection in 5XFAD mice and throughout the course of prion disease, preventing behavioural deficits and neuronal loss and significantly prolonging survival. In contrast, knockdown of RBM3 exacerbated synapse loss in both models and accelerated disease and prevented the neuroprotective effects of cooling. Thus, deficient synapse regeneration, mediated at least in part by failure of the RBM3 stress response, contributes to synapse loss throughout the course of neurodegenerative disease. The data support enhancing cold-shock pathways as potential protective therapies in neurodegenerative disorders

    Assessment of Aphasia Across the International Classification of Functioning, Disability and Health Using an iPad-Based Application

    Full text link
    © 2017, Mary Ann Liebert, Inc. Background: Access2Aphasia™ is an iPad™-based aphasia assessment application that enables real-time audiovisual communication between people with aphasia (PWA) and speech-language pathologists (SLPs), and the use of supported conversation techniques. This study aimed to establish the reliability of aphasia assessment across the International Classification of Functioning, Disability and Health (ICF) using Access2Aphasia, and compare it with face-to-face (FTF) assessment. Consumer perspectives of Access2Aphasia were also examined. Materials and Methods: Thirty PWA were randomized into two conditions: online-led and FTF assessment. Participants in the online-led group were assessed remotely using Access2Aphasia™ in their own homes, while an FTF SLP scored silently simultaneously. Participants in the FTF group were assessed FTF using standard administration materials. Assessment included two subtests of the Psycholinguistic Assessment of Language Processing Activities (PALPA) and the Assessment of Living with Aphasia (ALA) to allow for outcomes to be captured across the ICF domains. Consumer perspectives on Access2Aphasia were obtained from both PWA and research SLPs in the online-led group. Results: Kappa statistics indicated moderate to almost perfect agreement between online and FTF SLPs (k = 0.71-1.00). Intrarater and interrater reliability was excellent (ICC = 0.99-1.00) and equivalent for the online-led and FTF conditions. Both PWA and research SLPs in the online-led group reported being satisfied with the experience overall, with suggestions provided by research SLPs to improve Access2Aphasia. Conclusion: This study supports the provision of iPad-based aphasia assessments across the ICF in the online environment, with comparable reliability to FTF assessments. Future research is warranted to support the development of iPad-based aphasia assessment and treatment as an alternative mode of service delivery to PWA
    corecore