| 研究実績の概要 |
The accumulating evidence suggests glial dysfunction is involved in the pathogenesis of the autism spectrum disorders (ASDs). Lagged technological availability limited the detailed investigation of glial involvement in the development and progression of ASDs, which has complex multimodal signaling mechanisms underlying cellular, circuit and behavioral response.
Here, we further innovated multifunctional fibers, which integrate electrical, optical and/or chemical components into a single flexible polymer fiber and pioneered the backend interface to establish the straightforward connection with standard biological experimental setups. Such technological advancements provide easy access to the biological systems and allow us to evaluate the dynamics of astrocyte, one of type of glial cells, in mediating neural local and circuit level response underlying anxious phenotype of the ASDs.
We have been able to identify that astrocyte are strongly coupled with local neuronal dynamics, and manipulation of astrocytic activities can also cause changes of information flow among neural circuits across long-range brain regions, particularly prefrontal cortex and amygdala, which are important for regulating anxious behaviors in ASD.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
By applying the fibers-based technological innovations in the transgenic mouse model system, we have been able to evaluate the astrocyte involvement in mediating neural local and circuit level response underlying anxious phenotype of the ASDs. We found that astrocytes activities can affect both local neuronal responses, and also neural circuit oscillation and synchronization, which further regulates the behavioral output. More specifically, via particular optogenetic manipulation of astrocyte, either anxiogenic or anxiolytic effect could be produced. The results suggested technological innovations could advance our understanding of pathological causes of ASDs from neurocentric view to a more integrated manner with astrocyte involved.
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| 今後の研究の推進方策 |
We have successfully demonstrated the usefulness of the fiber-based technologies in studying astrocyte involvement in neurodevelopment disorder, ASDs. In order to further investigate the pathogenesis of the disease and seek the therapeutic strategies of the ASDs with astrocyte as the target, we will further stretch the functional boundaries of fibers with chemical sensing component with other standard functions as a tool to study astrocyte-neuron interaction in ASD, this will allow us to pinpoint the pathological molecules, that lead to the malfunction of the astrocyte and further impair normal neural development and dynamics. This will help pave the way to develop efficient pharmacological interventions for ASDs.
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