Editors' ChoiceNeuroscience

Stress Stops the Blood from Flowing

Sci. Signal.  27 May 2014:
Vol. 7, Issue 327, pp. ec140
DOI: 10.1126/scisignal.2005510

Chronic environmental stress alters brain activity leading to psychiatric symptoms such as anxiety and depression. Neurovascular coupling refers to the process in which neuronal activity temporarily increases local blood flow to meet increased metabolic demand. Neuronal depolarization evokes a Ca2+ wave in astrocytes, which are part of the blood-brain barrier, and causes them to release K+ into the extracellular space. High K+ stimulates inward-rectifying K+ (KIR) channels on smooth muscle cells of intracerebral arterioles to promote relaxation and thus vasodilation. Longden et al. found that neurovascular coupling was disrupted in rats exposed to a series of different environmental stressors for 7 days. Compared with those from control rats, arterioles in the amygdala (a brain region that responds to stress) in cultured brain slices of stressed rats had reduced dilation in response to electrical field stimulation or application of high bath concentrations of K+. Inhibition of KIR channels blocked dilation of arterioles in slices from control but not stressed rats. Moreover, arterioles of stressed rats had reduced expression of the gene encoding KIR2.2, and electrophysiological studies of myocytes isolated from the arterioles from the amygdala of stressed rats were consistent with a reduction in the number of functional channels. Arterioles in electrically stimulated brain slices of nonstressed mice injected with the glucocorticoid receptor agonist corticosterone (a circulating hormone that is increased by stress) had less dilation compared with those from nonstressed mice injected with the vehicle control. In contrast, injecting stressed rats with the glucocorticoid receptor antagonist RU486 prevented stress from reducing arteriole dilation. Thus, in addition to the morphological and molecular changes that occur in neurons, reduced neurovascular coupling may also contribute to neurological and behavioral symptoms that occur in response to chronic environmental stress.

T. A. Longden, F. Dabertrand, D. C. Hill-Eubanks, S. E. Hammack, M. T. Nelson, Stress-induced glucocorticoid signaling remodels neurovascular coupling through impairment of cerebrovascular inwardly rectifying K+ channel function. Proc. Natl. Acad. Sci. U.S.A. 111, 7462–7467 (2014). [Abstract] [Full Text]