* Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders.
- Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there is no effective treatment for these disorders. Cerebellar neuropathology is common in FASD and causes aberrant cognitive and motor function. Ethanol-induced neuroinflammation is believed to contribute to neuropathological sequelae of FASD, and was previously demonstrated in the cerebellum in animal models of FASD. We now demonstrate neuroinflammation persists in the cerebellum several days following cessation of ethanol treatment in an early postnatal mouse model, with meaningful implications for timing of therapeutic intervention in FASD. We also demonstrate by Sholl analysis that ethanol decreases ramification of microglia cell processes in cells located near the Purkinje cell layer but not those near the external granule cell layer. Ethanol did not alter the expression of anti-inflammatory molecules or molecules that constitute NLRP1 and NLRP3 inflammasomes. Interestingly, ethanol decreased the expression of IL-23a (P19) and IL-12Rβ1 suggesting that ethanol may suppress IL-12 and IL-23 signaling. Fractalkine-fractalkine receptor (CX3CL1-CX3CR1) signaling is believed to suppress microglial activation and our demonstration that ethanol decreases CX3CL1 expression suggests that ethanol modulation of CX3CL1-CX3CR1 signaling may contribute to cerebellar neuroinflammation and neuropathology. We demonstrate ethanol alters the expression of specific molecules in the cerebellum understudied in FASD, but crucial for immune responses. Ethanol increases the expression of NOX-2 and NGP and decreases the expression of RAG1, NOS1, CD59a, S1PR5, PTPN22, GPR37, and Serpinb1b. These molecules represent a new horizon as potential targets for development of FASD therapy.
=>発達, 開発, 産物, 進展
Overview of noun development
The noun development has 9 senses (first 7 from tagged texts)
1. (52) development -- (act of improving by expanding or enlarging or refining; "he congratulated
them on their development of a plan to meet the emergency"; "they funded research and development")
2. (46) development, evolution -- (a process in which something passes by degrees to a different
stage (especially a more advanced or mature stage); "the development of his ideas took many years";
"the evolution of Greek civilization"; "the slow development of her skill as a writer")
3. (11) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of
an individual organism growing organically; a purely biological unfolding of events involved in an
organism changing gradually from a simple to a more complex level; "he proposed an indicator of
osseous development in children")
4. (9) development -- (a recent event that has some relevance for the present situation; "recent
developments in Iraq"; "what a revolting development!")
5. (7) exploitation, development -- (the act of making some area of land or water more profitable or
productive or useful; "the development of Alaskan resources"; "the exploitation of copper deposits")
6. (6) development -- (a district that has been developed to serve some purpose; "such land is
practical for small park developments")
7. (4) development -- (a state in which things are improving; the result of developing (as in the
early part of a game of chess); "after he saw the latest development he changed his mind and became
a supporter"; "in chess your should take care of your development before moving your queen")
8. development, developing -- (processing a photosensitive material in order to make an image
visible; "the development and printing of his pictures took only two hours")
9. development -- ((music) the section of a composition or movement (especially in sonata form)
where the major musical themes are developed and elaborated)
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