Astrocytes contrbute on the cellular and molecular mechansms asso

Astrocytes contrbute to your cellular and molecular mechansms assocated wth whte matter njury observed following chronchypoxa,even so various of cell forms ncludng olgodendrocytes and ther progentors may also be nvolved.We are presently analyznghypoxa nduced injury to your olgodendrocyte lneage our anmal model of chronc pernatalhypoxa.Our prelmnary final results show that olgodendrocyte death takes place after the frst week ofhypoxa.Our studes also demonstrate that far more mature stages in the olgodendrocyte lneage are partcularly vulnerable tohypoxa nduced toxcty.other designs of pernatal branjury, ncludnghypoxa schema andhyperoxa nduced njury, thas beedemonstrated that late olgodendrocyte progentors are most vulnerable to njury.For that reason, t appears that dfferent kinds of nsults to selleck chemical the developng whte matter have an effect on dstnct phases in the olgodendrocyte lneage.Future expermental analyss wl defne the dfferent cellular and molecular mechansms that underle whte matter njury chronchypoxa,hypoxa schema andhyperoxa nduced njury for the developng bran.
Our fndng that expressoof GLAST and GLT inhibitor Nutlin-3 1 s decreased afterhypoxa s suggestve that modifications the concentratoof extracellular glutamate lkely arise the whte matter envronment.What are the physologcal consequences ofhypoxa nduced reductoastrocytc glutamate uptake the presence of extra glutamate, olgodendrocytes and ther progentors are broken like a consequence of more than actvatoof AMPA receptors and subsequent Ca2 nflux, whch ultmately triggers exctotoxcty.effectively establshed that glutamate vescles are released from unmyelnated axons the whte matter and ths s a potental supply of extra glutamate thehypoxc anmal.We demonstrate that vvo at P11 each GLAST and GLT 1 expressoare sgnfcantly reduced the whte matter, and that D aspartate uptake whte matter glosomes s sgnfcantly decreased afterhypoxa.These fndngs strongly propose that astrocyte mpared abty to clear glutamate afterhypoxa would cause excess glutamate the extracellular room, whch turcauses exctotoxc damage to mmature olgodendrocytes and or prevents ther maturatoto myelnatng olgodendrocytes.
concluson, dysregulatoof glutamatehomeostass whte matter astrocytes afterhypoxa http://t.co/MfAIst4oCe

— Lasyaf Hossain (@lasyafhossain) November 8, 2013

s most lkely one of the contrbutng factors underlyng olgodendrocyte pathology afterhypoxc njury.the present study, we demonstrate that the cellular response of astrocytes tohypoxc njury vvo nvolves not only a reductoglutamate transporter expressothe developng whte matter whch turlkely affects glutamatehomeostass but also attenuatoof JAK STAT sgnalng resultng ammature phenotype, and these two responses are lkely to be causally related.Defnnghow the JAK STAT pathway regulates GLAST expressowl be mportant to develomolecular therapeutc targets to promote neuroprotectoor preventoof injury for the premature bran.

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