Understanding higher level gait disturbances in mild dementia in order to improve rehabilitation: ‘Last in-first out’

Predicting and anticipating disturbances in higher level gait is particularly relevant for patients with dementia as higher level gait appears to be closely related to higher level cognitive functioning. A phenomenon that could contribute to the understanding and prediction of disturbances in higher level gait and gait-related motor activity in the various subtypes of dementia is paraphrased as ‘last in-first out’. ‘Last in-first out’ refers to the principle that neural circuits that mature late in development are the most vulnerable to neurodegeneration. The strength of relating symptoms to the ‘last in-first out’ principle is that a future symptom can be predicted and anticipated in a therapeutic way, even if the disease process has not already started.Therefore, the aim of this review is to provide new strategies for rehabilitation of higher level gait disturbances in dementia based upon the ‘last in-first out’ principle. These new strategies emerge from five neural networks: the superior longitudinal fasciculus, the uncinate fasciculus, the fronto-cerebellar and fronto-striatal connections, and the cingulum.     

Polychromatic immunophenotypic characterization of T cell profiles among HIV-infected patients experiencing immune reconstitution inflammatory syndrome (IRIS)

Objective  

To immunophenotype CD4⁺ and CD8⁺ T cell sub-populations in HIV-associated immune reconstitution inflammatory syndrome (IRIS).     

Testosterone affects language areas of the adult human brain

Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc .     

Separable effects of priming and imageability on word processing: an ERP study

Concrete, highly imageable words (e.g. banana) are easier to understand than abstract words for which it is difficult to generate an image (e.g. justice). This effect of concreteness or imageability has been taken by some as evidence for the existence of separable verbal- and image-based semantic systems. Instead, however, effects of concreteness may result from better associations to relevant contextual representations for concrete than for abstract words within a single semantic system. In this study, target words of high and low imageability were preceded by supportive (related) or non-supportive (unrelated) context words. The influence of contextual support on the imageability effect was measured by recording event-related brain potentials (ERPs) to the high and low imageable target words in both context conditions. The topographic distributions of the ERPs elicited by the high versus low imageable target words were found to be different, and this effect was independent of contextual support. These data are consistent with the idea that distinct verbal- and image-based semantic codes exist for word representations, and that as a result, concrete words that are highly imageable can be understood more easily.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.