Atmospheric methane levels increased over geological formations in Northern Siberia following a heat wave in 2020, suggesting that permafrost thaw releases methane from reservoirs.
Image credit: Wikimedia Commons.
Edited by Richard W. Aldrich, The University of Texas at Austin, Austin, TX, and approved April 11, 2014 (received for review January 29, 2014)
Significance
When neurons become active, they signal to local arterioles via intermediate glial cells, called astrocytes, to evoke dilation. This increases local blood flow and provides the oxygen and glucose necessary to support ongoing neuronal function. This process is termed neurovascular coupling. We demonstrate that chronic stress—which is a contributing factor for many diseases—impairs neurovascular coupling in the amygdala, a region involved in stressor processing. Our results further indicate that this dysfunction is due to the loss of arteriolar inwardly rectifying potassium (K+) channel function, which makes vessels less able to respond to vasodilatory K+ ions released by astrocytes during periods of increased neuronal activity. This neurovascular coupling impairment may contribute to the pathology of a range of brain disorders.
Abstract
Studies of stress effects on the brain have traditionally focused on neurons, without considering the cerebral microcirculation. Here we report that stress impairs neurovascular coupling (NVC), the process that matches neuronal activity with increased local blood flow. A stressed phenotype was induced in male rats by administering a 7-d heterotypical stress paradigm. NVC was modeled by measuring parenchymal arteriole (PA) vasodilation in response to neuronal stimulation in amygdala brain slices. After stress, vasodilation of PAs to neuronal stimulation was greatly reduced, and dilation of isolated PAs to external K+ was diminished, suggesting a defect in smooth muscle inwardly rectifying K+ (KIR) channel function. Consistent with these observations, stress caused a reduction in PA KIR2.1 mRNA and smooth muscle KIR current density, and blocking KIR channels significantly inhibited NVC in control, but not in stressed, slices. Delivery of corticosterone for 7 d (without stressors) or RU486 (before stressors) mimicked and abrogated NVC impairment by stress, respectively. We conclude that stress causes a glucocorticoid-mediated decrease in functional KIR channels in amygdala PA myocytes. This renders arterioles less responsive to K+ released from astrocytic endfeet during NVC, leading to impairment of this process. Because the fidelity of NVC is essential for neuronal health, the impairment characterized here may contribute to the pathophysiology of brain disorders with a stress component.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: Mark.Nelson{at}uvm.edu.
Author contributions: T.A.L., S.E.H., and M.T.N. designed research; T.A.L. and F.D. performed research; T.A.L. analyzed data; and T.A.L., D.C.H.-E., S.E.H., and M.T.N. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1401811111/-/DCSupplemental.
Stress remodels neurovascular coupling
Article Classifications
- Biological Sciences
- Neuroscience
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Pottery, burnt clay, and burnt flint from Jordan dated from 7752 BCE to 5069 BCE yielded a record of variations in Earth’s magnetic field strength during the Neolithic period.
Image credit: Thomas E. Levy.
Mechanics of ant tunneling could inspire the development of improved robotic mining techniques.
Image credit: Jose E. Andrade and David R. Miller (California Institute of Technology, Pasadena, CA).
When it comes to potential geoengineering initiatives, researchers and policymakers need to know what to study—and when to stop.
Image credit: Shutterstock/Venera Salman.
The gasdermin protein family has unexpectedly ancient origins.
Image credit: Alex Johnson.