Role on Blood Pressure Regulation of Noradrenergic Neurons Originating from the Locus Coeruleus in the Kyoto-Wistar Rat

Ogawa, Mitsuhiro; Fujita, Yasuhiko; Níwa, Masami; Takami, Naoko; Ozaki, Masayori

doi:10.1536/ihj.18.586

Cited by 9 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As LC is critically involved in orchestrating the central stress responses involving cardiovascular and stereotypical manifestations (Elam et al., 1984, Ogawa et al., 1977, Saran et al., 1978), we wanted to explore whether LC loss of ASL could contribute to the hypertension observed in mice and humans with ASLD. Using continuous blood pressure telemetric measurements, and consistent with our previous reports, we found that endothelial-ASL cKO mice ( Asl f/f ;Cdn Cre +/− ) have a significantly higher blood pressure (Kho et al., 2018).…”

Section: Resultsmentioning

confidence: 99%

ASL Metabolically Regulates Tyrosine Hydroxylase in the Nucleus Locus Coeruleus

Lerner¹,

Anderzhanova

Verbitsky

et al. 2019

Cell Reports

View full text Add to dashboard Cite

SummaryPatients with germline mutations in the urea-cycle enzyme argininosuccinate lyase (ASL) are at risk for developing neurobehavioral and cognitive deficits. We find that ASL is prominently expressed in the nucleus locus coeruleus (LC), the central source of norepinephrine. Using natural history data, we show that individuals with ASL deficiency are at risk for developing attention deficits. By generating LC-ASL-conditional knockout (cKO) mice, we further demonstrate altered response to stressful stimuli with increased seizure reactivity in LC-ASL-cKO mice. Depletion of ASL in LC neurons leads to reduced amount and activity of tyrosine hydroxylase (TH) and to decreased catecholamines synthesis, due to decreased nitric oxide (NO) signaling. NO donors normalize catecholamine levels in the LC, seizure sensitivity, and the stress response in LC-ASL-cKO mice. Our data emphasize ASL importance for the metabolic regulation of LC function with translational relevance for ASL deficiency (ASLD) patients as well as for LC-related pathologies.

show abstract