Increased Brain Neurotensin and NTSR2 Lead to Weak Nociception in NTSR3/Sortilin Knockout Mice

• Published in: Frontiers in neuroscience Vol. 10; p. 542
• Main Authors: Devader, Christelle, Moreno, Sébastien, Roulot, Morgane, Deval, Emmanuel, Dix, Thomas, Morales, Carlos R, Mazella, Jean
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 24.11.2016; Frontiers Media S.A
• Subjects: Antipsychotics; Brain; Cellulose acetate; Experiments; knockout gene; Memory; Neural coding; Neuroscience; Neurosciences; Neurotensin; Nociception; Pain; Pain perception; Proteins; receptor; Rodents; sortilin; Canada; Montreal Quebec Canada; France; United States > US; sortilin; nociception; neurotensin; receptor; knockout gene
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2016.00542

The neuropeptide neurotensin (NT) elicits numerous pharmacological effects through three different receptors (NTSR1, NTSR2, and NTSR3 also called sortilin). Pharmacological approaches and generation of NTSR1 and NTSR2-deficient mice allowed to determine the NT-induced antipsychotic like behavior, the inhibitory of weak fear memory and the nociceptive signaling in a rat formalin tonic pain model to NTSR1. Conversely, the effects of NT on thermal and tonic nociceptions were mediated by NTSR2. However, the role of NTSR3/sortilin on the neurotensinergic system was not investigated. Here, by using C57Bl/6J mouse model in which the gene coding for NTSR3/sortilin has been inactivated, we observed a modification of the expression of both NTSR2 and NT itself. Quantitative PCR and protein expression using Western blot analyses and AlphaLisa™ technology resulted in the observation that brain NTSR2 as well as brain and blood NT were 2-fold increased in KO mice leading to a resistance of these mice to thermal and chemical pain. These data confirm that NTSR3/sortilin interacts with other NT receptors (i.e., NTSR2) and that its deletion modifies also the affinity of this receptor to NT.