Modulating the water channel AQP4 alters miRNA expression, astrocyte connectivity and water diffusion in the rodent brain
Sci Rep. 2018-03-08; 8(1):
DOI: 10.1038/s41598-018-22268-y
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Jullienne A(1)(2), Fukuda AM(1)(2), Ichkova A(3), Nishiyama N(2), Aussudre J(3), Obenaus A(1)(4), Badaut J(5)(6)(7).
Author information:
(1)Basic Sciences Department, Loma Linda University, Loma Linda, CA, 92354, USA.
(2)Department of Physiology, Loma Linda University, Loma Linda, CA, 92354, USA.
(3)CNRS-UMR 5287, University of Bordeaux, 33076, Bordeaux, France.
(4)Department of Pediatrics, University of California Irvine, Irvine, CA, 92697, USA.
(5)Basic Sciences Department, Loma Linda University, Loma Linda, CA, 92354, USA. .
(6)Department of Physiology, Loma Linda University, Loma Linda, CA, 92354, USA. .
(7)CNRS-UMR 5287, University of Bordeaux, 33076, Bordeaux, France. .
Aquaporins (AQPs) facilitate water diffusion through the plasma membrane. Brain
aquaporin-4 (AQP4) is present in astrocytes and has critical roles in normal and
disease physiology. We previously showed that a 24.9% decrease in AQP4 expression
after in vivo silencing resulted in a 45.8% decrease in tissue water mobility as
interpreted from magnetic resonance imaging apparent diffusion coefficients
(ADC). Similar to previous in vitro studies we show decreased expression of the
gap junction protein connexin 43 (Cx43) in vivo after intracortical injection of
siAQP4 in the rat. Moreover, siAQP4 induced a loss of dye-coupling between
astrocytes in vitro, further demonstrating its effect on gap junctions. In
contrast, silencing of Cx43 did not alter the level of AQP4 or water mobility
(ADC) in the brain. We hypothesized that siAQP4 has off-target effects on Cx43
expression via modification of miRNA expression. The decreased expression of Cx43
in siAQP4-treated animals was associated with up-regulation of miR224, which is
known to target AQP4 and Cx43 expression. This could be one potential molecular
mechanism responsible for the effect of siAQP4 on Cx43 expression, and the
resultant decrease in astrocyte connectivity and dramatic effects on ADC values
and water mobility.