Abstract
Neurovascular coupling ensures rapid and precise delivery of O2 and nutrients to active brain regions. Chronic stress is known to disturb neurovascular signaling with grave effects on brain integrity. We hypothesized that stress-induced neurovascular disturbances depend on stress susceptibility. Wistar male rats were exposed to 8 weeks of chronic mild stress. Stressed rats with anhedonia-like behavior and with preserved hedonic state were identified from voluntary sucrose consumption. In brain slices from nonstressed, anhedonic, and hedonic rats, neurons and astrocytes showed similar intracellular Ca2+ responses to neuronal excitation. Parenchymal arterioles in brain slices from nonstressed, anhedonic, and hedonic rats showed vasodilation in response to neuronal excitation. This vasodilation was dependent on inward rectifying K+ channel (Kir2) activation. In hedonic rats, this vasodilation was transient and followed by vasoconstriction insensitive to Kir2 channel inhibition with 100 µM BaCl2. Isolated arteries from hedonic rats showed increased contractility. Elevation of bath K+ relaxed isolated middle cerebral arteries in a concentration-dependent and Kir2-dependent manner. The vasorelaxation to 20–24 mM K+ was reduced in arteries from hedonic rats. The expression of voltage-gated K+ channels, Kv7.4, was reduced in the cerebral arteries from hedonic rats, whereas the expression of arterial inward-rectifying K+ channels, Kir2.1 was similar to that of nonstressed and anhedonic rats. We propose that preserved hedonic state is associated with increased arterial contractility caused by reduced hyperpolarizing contribution of Kv7.4 channels leading to biphasic cerebrovascular responses to neuronal excitation. These findings reveal a novel potential coping mechanism associated with altered neurovascular signaling.
Acknowledgments
We thank Jane Holbaek Roenn for technical assistance with Western blot analysis.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Christian Staehr
Christian Staehr, M.D. recently graduated as a medical doctor from Aarhus University (2021). In his PhD, he studies brain blood flow and neurovascular coupling in health and disease. His research suggests that restoration of balanced neurovascular coupling may be a novel treatment target in numerous neurological disorders.
Elena V. Bouzinova
Elena Bouzinova has PhD in neuroscience from Lomonosov Moscow State University (1998) and PhD in membrane transport from Aarhus University (2007). She is studying the devastating effects of chronic stress and neuronal dysfunction behind it in various animal models.
Ove Wiborg
Ove Wiborg, PhD from Aarhus University (1989). He is an Associate Professor at Aalborg University and has his research interest in neurobiology of Major Depression, Memory Loss, Alzheimer's Disease, and Dementia.
Vladimir V. Matchkov
Vladimir Matchkov has his PhD from Lomonosov Moscow State University (1998) and DMSc from Aarhus University (2010). Since 2010, he is an Associate Professor at Aarhus University, Health. His research addresses the comorbidity of neuronal disorders and disturbances in cerebral perfusion, with a focus of dysbalanced neurovascular coupling signaling.