Circadian misalignment decreases glutamatergic activity in the nucleus of the solitary tract resulting in increased blood pressure
Authors: Lopez Vasquez Maria Celeste , Conviser Jason , Nguyen Trinh , Rajendran Yoshna , Crowthers Raymond , Ghiarone Thaysa , Silva Kleiton , Martinez Diana 
Published: May 2023

The nucleus of the solitary tract (nTS) is the initial termination site for cardiorespiratory afferents, and thus is a critical central region for control of blood pressure. Blood pressure follows a 24-hour cycle; dips during sleep and peaks during wake. Sleep disturbances including work outside of normal hours (shift work) induces a misalignment between the endogenous circadian system and the sleep/wake cycle, known as circadian misalignment (CM). CM raises the risk of elevated blood pressure. Our lab has shown that nTS glutamatergic activity conversely fluctuates with 24-hour blood pressure pattern, decreasing at wake (increased blood pressure), and increasing at sleep (lower blood pressure). However, how CM disrupts the 24-hour pattern of nTS glutamate activity is not known. Our goal is to determine the role of the nTS in elevated blood pressure due to CM. To address this, we used a combination of electrophysiology, molecular methods, immunohistochemistry, acute cardiorespiratory recordings, and 24/7 telemetry. We exposed 7–11 week-old male Sprague Dawley rats to an established model of CM. The CM protocol is 22 days of 6-h light (L) phase advances every 2 days. Control rats were exposed to 22 days of standard 12:12 LD (light:dark). After 22 days of the CM protocol, blood pressure is elevated in both the active and inactive period in comparison to control rats. Measurements, for other parameters, were compared at four times (ZT0, ZT6, ZT12, ZT18) except for electrophysiological recordings. We examined the relationship between increased blood pressure in CM and glutamatergic activity. First, we used coronal slices containing the nTS (at the level of area postrema) from perfused animals. Active glutamatergic neurons (denoted by cFos expression colocalized with Glu marker CAMKII) decreased during the active period in comparison to the inactive period. Glutamatergic cell activation was not only decreased in CM but did not differ significantly between time points. To examine if CM effects correlate with channel subunit expression, we used western blot. Interestingly, in CM glutamatergic receptor subunit (GluA1) expression was lower at all time points in comparison to control. In control, during the active period, the resting membrane potential of nTS neurons were hyperpolarized in comparison to CM. This led to a significant decrease in spontaneous excitatory post-synaptic currents in nTS neurons during the active period in CM. The data indicate that glutamatergic activity decreased during the active period when blood pressure was higher in circadian misalignment. Taken together, these results suggest that the nTS glutamatergic circadian pattern, may be disrupted in circadian misalignment, and contribute to the increased blood pressure in a model of shift work.

DM NIH LRP 1L40HL165612-01, DM CMSRU Internal Award, NIH NIGMS T34GM136492

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.