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P2‐081: CREB regulates the expression of neuronal glucose transporter 3: A mechanism leading to impaired brain glucose uptake in Alzheimer's disease
Author(s) -
Jin Nana,
Qian Wei,
Yin Xiaomin,
Iqbal Khalid,
GrundkeIqbal Inge,
Gong ChengXin,
Liu Fei
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.785
Subject(s) - glut3 , creb , glucose transporter , calpain , hyperphosphorylation , chromatin immunoprecipitation , glucose uptake , biology , glut1 , microbiology and biotechnology , gene expression , phosphorylation , transcription factor , promoter , endocrinology , biochemistry , gene , enzyme , insulin
laevis oocytes exposed to amyloid-b aggregate generated oscillatory electric activity (blips) that was recorded by two-microelectrode voltageclamp. Results: The cells exhibited a series of “spontaneous” blips ranging in amplitude from 3.86 0.9 nA at the beginning of the recordings to 6.86 1.7 nA after 15 min of exposure to 1 mMaggregate. These blips were similar in amplitude to those induced by the channel-forming antimicrobial agents amphotericin B (7.86 1.2 nA) and gramicidin (6.36 1.1 nA). The amyloid aggregate-induced currents were abolished when extracellular calcium was removed from the bathing solution, suggesting a central role for this cation in generating the spontaneous electric activity. The amyloid aggregate also affected the calcium-dependent chloride currents of oocytes, as shown by increased amplitude of the transient-outward chloride current (Tout) and the serum-activated, oscillatory chloride currents. Electron microcopy revealed that amyloid aggregate induce the dissociation of the follicular cells that surround the oocyte, thus leading to a failure in the electro-chemical communication between these cells. This was also evidenced by the suppression of the oscillatory calcium-dependent ATP-currents, which require proper coupling between oocytes and the follicular cell layer. Conclusions: These observations, made using the X. laevis oocytes as a versatile experimental model, may help to understand the effects of amyloid aggregate on cellular communication.