Regional registration of [6-(14)C]glucose metabolism during brain activation of α-syntrophin knockout mice.
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 [(14)C]metabolites during sensory stimulation. Conscious KO and wild-type mice were pulse-labeled with [6-(14)C] glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [(14)C]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.
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Nancy F
NF
Cruz
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Kelly K
KK
Ball
Department of Physiology and Biophysics, University of Washington, Seattle, Washington, USA.
Stanley C
SC
Froehner
Department of Physiology and Biophysics, University of Washington, Seattle, Washington, USA.
Marvin E
ME
Adams
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Gerald A
GA
Dienel
D000161:Acoustic Stimulation; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000378:metabolism*; D010812:Physical Stimulation
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D002135:Calcium-Binding Proteins; D002250:Carbon Radioisotopes; D008565:Membrane Proteins; D009124:Muscle Proteins; C091825:syntrophin alpha1; D005947:Glucose
aquaporin4; brain activation; glucose; lactate release; α‐syntrophin knockout