Identification of a population of peripheral sensory neurons that regulates blood pressure

Chiara Morelli; Laura Castaldi; Sam J Brown; Lina L Streich; Alexander Websdale; Francisco J Taberner; Blanka Cerreti; Alessandro Barenghi; Kevin M Blum; Julie Sawitzke; Tessa Frank; Laura K Steffens; Balint Doleschall; Joana Serrao; Denise Ferrarini; Stefan G Lechner; Robert Prevedel; Paul A Heppenstall

doi:10.1016/j.celrep.2021.109191

Identification of a population of peripheral sensory neurons that regulates blood pressure

Cell Rep. 2021 Jun 1;35(9):109191. doi: 10.1016/j.celrep.2021.109191.

Authors

Chiara Morelli¹, Laura Castaldi², Sam J Brown³, Lina L Streich⁴, Alexander Websdale³, Francisco J Taberner⁵, Blanka Cerreti³, Alessandro Barenghi³, Kevin M Blum⁶, Julie Sawitzke³, Tessa Frank³, Laura K Steffens⁷, Balint Doleschall³, Joana Serrao³, Denise Ferrarini³, Stefan G Lechner⁸, Robert Prevedel⁹, Paul A Heppenstall¹⁰

Affiliations

¹ EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany; Collaboration for joint PhD degree between EMBL Heidelberg, Heidelberg, Germany, and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany.
² EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany.
³ EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy.
⁴ Collaboration for joint PhD degree between EMBL Heidelberg, Heidelberg, Germany, and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
⁵ EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy; Institute of Pharmacology, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
⁶ Center for Regenerative Medicine, the Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Biomedical Engineering, the Ohio State University, Columbus, OH, USA.
⁷ Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
⁸ Institute of Pharmacology, Heidelberg University, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
⁹ EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Developmental Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
¹⁰ EMBL Rome, Via Ramarini 32, Monterotondo 00015, Italy; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany. Electronic address: paul.heppenstall@sissa.it.

Abstract

The vasculature is innervated by a network of peripheral afferents that sense and regulate blood flow. Here, we describe a system of non-peptidergic sensory neurons with cell bodies in the spinal ganglia that regulate vascular tone in the distal arteries. We identify a population of mechanosensitive neurons, marked by tropomyosin receptor kinase C (TrkC) and tyrosine hydroxylase in the dorsal root ganglia, which projects to blood vessels. Local stimulation of TrkC neurons decreases vessel diameter and blood flow, whereas systemic activation increases systolic blood pressure and heart rate variability via the sympathetic nervous system. Ablation of the neurons provokes variability in local blood flow, leading to a reduction in systolic blood pressure, increased heart rate variability, and ultimately lethality within 48 h. Thus, a population of TrkC⁺ sensory neurons forms part of a sensory-feedback mechanism that maintains cardiovascular homeostasis through the autonomic nervous system.

Keywords: DRG; TH; TrkC; blood pressure; cardiovascular homeostasis; peripheral nervous system.

MeSH terms

Animals
Behavior, Animal
Blood Pressure / physiology*
Fluorescein / metabolism
Ganglia, Spinal / physiology
Heart Rate / physiology
Mice, Transgenic
Receptor, trkC / metabolism
Sensory Receptor Cells / physiology*

Substances

Receptor, trkC
Fluorescein