P2‐081: CREB regulates the expression of neuronal glucose transporter 3: A mechanism leading to impaired brain glucose uptake in Alzheimer's disease

Abstract

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.