Fig. 4: Genetic knockdown of sodium bicarbonate cotransporter 1 (NBCe1) in astrocytes blocks the neurovascular response in the somatosensory cortex in mice.
From: CO2 signaling mediates neurovascular coupling in the cerebral cortex
a Schematic depiction of the neurovascular unit illustrating disrupted CO2/HCO3− transport in astroglial endfeet in conditions of NBCe1 deficiency. b Changes in tissue PO2 (PtO2) and the neuronal activity in the S1FL cortical region of mice were recorded using fast scan cyclic voltammetry. The carbon fiber microelectrode (CFM) was placed in the S1FL region. The forepaw was stimulated electrically to activate the somatosensory pathways. c Knockdown of NBCe1 expression in cortical astrocytes. Representative confocal images illustrating immunohistochemical detection of NBCe1 in the cortex of NBCe1flox/flox:GLASTCreERT2/+ mice treated with the vehicle (oil) or tamoxifen. Tamoxifen treatment of NBCe1flox/flox:GLASTCreERT2/+ mice resulted in a mosaic pattern of NBCe1 expression. Staining was repeated in four animals from each experimental group with similar result. Scale bars = 50 µm. d, e Activity in the open field exhibited by NBCe1flox/flox:GLASTCreERT2/+ mice treated with vehicle, NBCe1flox/flox:GLAST+/+ mice (cre-negative) treated with tamoxifen, and NBCe1flox/flox:GLASTCreERT2/+ mice treated with tamoxifen. Mice with conditional NBCe1 knockdown in astrocytes displayed behavioral pattern (increased locomotor speed and vertical activity) consistent with the increased anxiety. f Time course of PtO2 changes in the S1FL region induced by activation of somatosensory pathways (electrical stimulation of the contralateral paw; 3 Hz, 1.5 mA) in NBCe1flox/flox:GLASTCreERT2/+ mice treated with the vehicle or tamoxifen and NBCe1flox/flox:GLAST+/+ mice treated with tamoxifen. NBCe1 knockdown in cortical astrocytes prevented the development of the neurovascular response. Traces illustrate averaged (mean values ± SEM) changes in PO2-sensitive current. g Summary data illustrating peak (measurements taken at the end of the stimulation period) and integral (area under the curve, AUC) changes in PO2, evoked in the S1FL region by electrical forepaw stimulation in NBCe1flox/flox:GLASTCreERT2/+ mice treated with the vehicle or tamoxifen, and NBCe1flox/flox:GLAST+/+ mice treated with tamoxifen. In the box-and-whisker plots the central dot indicates the mean, the central line indicates the median, the box limits indicate the upper and lower quartiles, and the whiskers show the minimum–maximum range of the data. Numbers in parentheses indicate sample sizes (number of animals per experimental group). P values, Kruskal–Wallis test followed by Dunn’s multiple comparison test. Source data are provided as a Source Data file.
