Abstract: The Sound of Vision project involves developing a sensory substitution device that is aimed at creating and conveying a rich auditory representation of the surrounding environment to the visually impaired. However, the feasibility of such an approach is strongly constrained by neural flexibility, possibilities of sensory substitution and adaptation to changed sensory input. We review evidence for such flexibility from various perspectives. We discuss neuroplasticity of the adult brain with an emphasis on functional changes in the visually impaired compared to sighted people. We discuss effects of adaptation on brain activity, in particular short-term and long-term effects of repeated exposure to particular stimuli. We then discuss evidence for sensory substitution such as Sound of Vision involves, while finally discussing evidence for adaptation to changes in the auditory environment. We conclude that sensory substitution enterprises such as Sound of Vision are quite feasible in light of the available evidence, which is encouraging regarding such projects.
Abstract: An important aspect of CNS disease and injury is the elevated expression of neuroimmune factors. These factors are thought to contribute to processes ranging from recovery and repair to pathology. The complexity of the CNS and the multitude of neuroimmune factors that are expressed in the CNS during disease and injury is a challenge to an understanding of the consequences of the elevated expression relative to CNS function. One approach to address this issue is the use of transgenic mice that express elevated levels of a specific neuroimmune factor in the CNS by a cell type that normally produces it. This approach can provide basic information about the actions of specific neuroimmune factors and can contribute to an understanding of more complex conditions when multiple neuroimmune factors are expressed. This review summarizes studies using transgenic mice that express elevated levels of IL-6, CCL2 or CXCL10 through increased astrocyte expression. The studies focus on the effects of these neuroimmune factors on synaptic function at the Schaffer collateral to CA1 pyramidal neuron synapse of the hippocampus, a brain region that plays a key role in cognitive function.
Abstract: The cytokines interleukin 13 and 4 share a common heterodimeric receptor and are important modulators of peripheral allergic reactions. Produced primarily by T-helper type 2 lymphocytes, they are typically considered as anti-inflammatory cytokines because they can downregulate the synthesis of T-helper type 1 pro-inflammatory cytokines. Their presence and role in the brain is only beginning to be investigated and the data collected so far shows that these molecules can be produced by microglial cells and possibly by neurons. Attention has so far been given to the possible role of these molecules in neurodegeneration. Both neuroprotective or neurotoxic effects have been proposed based on evidence that interleukin 13 and 4 can reduce inflammation by promoting the M2 microglia phenotype and contributing to the death of microglia M1 phenotype, or by potentiating the effects of oxidative stress on neurons during neuro-inflammation. Remarkably, the heterodimeric subunit IL-13Rα1 of their common receptor was recently demonstrated in dopaminergic neurons of the ventral tegmental area and the substantia nigra pars compacta, suggesting the possibility that both cytokines may affect the activity of these neurons regulating reward, mood, and motor coordination. In mice and man, the gene encoding for IL-13Rα1 is expressed on the X chromosome within the PARK12 region of susceptibility to Parkinson’s disease (PD). This, together with finding that IL-13Rα1 contributes to loss of dopaminergic neurons during inflammation, indicates the possibility that these cytokines may contribute to the etiology or the progression of PD.
Abstract: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, in which a small naturally unfolded protein α-synuclein plays an essential role. α-Synuclein belongs to a synuclein family comprising three members: α, β, and γ-synucleins associated with neurodegenerative and neoplastic diseases and involved in development. Several studies revealed that α-synuclein is present not only in the brain, but also in the skin and other peripheral tissues. This finding open a new approach to PD diagnosis based on the assay of α-synuclein from a biological sample of a living patient. Furthermore, PD is associated with an increased risk of skin melanoma. An important posttranslational modification of α-synuclein is phosphorylation at serine-129, which may convert the protein into pathological species both in PD and melanoma. Thus, analysis of phosphorylated α-synuclein might be an important diagnostic test for both diseases providing additional information about the mechanism of pathology.
Abstract: Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used for ELISAs of cytokines and growth factors. A single binge ethanol exposure resulted in low-level of microglial activation; however, a second binge potentiated the microglial response. Specifically, double binge rats had greater OX-42 immunoreactivity, increased ionized calcium-binding adapter molecule 1 (Iba-1+) cells, and upregulated tumor necrosis factor-α (TNF-α) compared with the single binge ethanol group. These data indicate that prior ethanol exposure potentiates a subsequent microglia response, which suggests that the initial exposure to alcohol primes microglia. In summary, repeated ethanol exposure, independent of other immune modulatory events, potentiates microglial activity.
Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine that not only plays major roles in the immune system, but also serves as a coordinator between the nervous and endocrine systems. IL-6 is produced in multiple cell types in the CNS, and in turn, many cells respond to it. It is therefore important to ascertain which cell type is the key responder to IL-6 during both physiological and pathological conditions. In order to test the role of astrocytic IL-6 in neuroinflammation, we studied an extensively-used animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), in mice with an IL-6 deficiency in astrocytes (Ast-IL-6 KO). Results indicate that lack of astrocytic IL-6 did not cause major changes in EAE symptomatology. However, a delay in the onset of clinical signs was observed in Ast-IL-6 KO females, with fewer inflammatory infiltrates and decreased demyelination and some alterations in gliosis and vasogenesis, compared to floxed mice. These results suggest that astrocyte-secreted IL-6 has some roles in EAE pathogenesis, at least in females.