Functional ultrasound imaging to study brain dynamics: Application of pharmaco-fUS to atomoxetine

Autor: Marco Valdebenito, Ludovic Venet, Benjamin Vidal, Mathieu Charvériat, Luc Zimmer, Marine Droguerre, Franck Mouthon
Přispěvatelé: Theranexus [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hospices Civils de Lyon (HCL)
Rok vydání: 2020
Předmět:
Zdroj: Neuropharmacology
Neuropharmacology, Elsevier, 2020, 179, pp.108273. ⟨10.1016/j.neuropharm.2020.108273⟩
ISSN: 1873-7064
0028-3908
DOI: 10.1016/j.neuropharm.2020.108273⟩
Popis: International audience; Highlights• A first evaluation of the potential of fUS during a pharmacological challenge.• ATX modulates cerebral blood volume in areas associated with visual processing.• fUS as a new step to move forwards new drugs to development in neurological disorders.Functional ultrasound (fUS) is a new tool enabling the imaging of brain activity through the regional monitoring of cerebral blood volume (CBV) dynamics. This innovative technique has not yet demonstrated its full potential in pharmacological applications and drug development. In the current proof-of-concept study, the impact of atomoxetine (ATX), a potent norepinephrine reuptake inhibitor and non-stimulant treatment marketed in attention-deficit/hyperactivity-disorder, was evaluated in anesthetized rat using pharmacological functional ultrasound (pharmaco-fUS) at increasing doses (0.3, 1 and 3 mg/kg). Using regions of interest (acute changes of CBV and functional connectivity) or pixel-based (general linear modeling and independent component analysis) analysis, we here demonstrated that ATX consistently displayed a hemodynamic effect in the visual cortex, the dentate gyrus and thalamus, especially visual areas such as lateral posterior thalamic nuclei and lateral geniculate nuclei (LGN). The time profile of ATX effects was dose-dependent, with fastest CBV increases at the highest dose, and longer CBV increases at the intermediate dose. Standardizing the use of pharmaco-fUS could improve our understanding of the mechanism of action of drugs active in the brain and might constitute a new step to move forward in drug development for neurological disorders.
Databáze: OpenAIRE