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Keywords:

  • α-syntrophin knockout;
  • aquaporin4;
  • brain activation;
  • glucose;
  • lactate release

Abstract

α-Syntrophin is a component of the dystrophin scaffold-protein complex that serves as an adaptor for recruitment of key proteins to the cytoplasmic side of plasma membranes. α-Syntrophin knockout (KO) causes loss of the polarized localization of aquaporin4 (AQP4) at astrocytic endfeet and interferes with water and K+ homeostasis. During brain activation, release of ions and metabolites from endfeet is anticipated to increase perivascular fluid osmolarity, AQP4-mediated osmotic water flow from endfeet, and metabolite washout from brain. This study tests the hypothesis that reduced levels of endfoot AQP4 increase retention of [14C]metabolites during sensory stimulation. Conscious KO and wild-type mice were pulse-labeled with [6-14C] glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [14C]metabolites in extracts, respectively. High-resolution autoradiographic assays detected a 17% side-to-side difference (p < 0.05) in inferior colliculus of KO mice, not wild-type mice. However, there were no labeling differences between KO and wild-type mice for five major HPLC fractions from four dissected regions, presumably because of insufficient anatomical resolution. The results suggest a role for AQP4-mediated water flow in support of washout of metabolites, and underscore the need for greater understanding of astrocytic water and metabolite fluxes.