Intense physical activity and dieting are core symptoms of anorexia nervosa (AN). Their combination evolves into compulsivity, leading the patient into an out-of-control spiral. AN patients exhibit an altered activation of nucleus accumbens (NAc), revealing a dysfunctional mesocorticolimbic reward circuitry in AN. Since evidence exists that a dysregulation of the glutamate system in the NAc influences reward and taking advantage of the activity-based anorexia (ABA) rat model, which closely mimics the hallmarks of AN, we investigated the involvement of the glutamatergic signaling in the NAc in this experimental model. We here demonstrate that food restriction causes hyperactive and compulsive behavior in rodents, inducing an escalation of physical activity, which results in dramatic weight loss. Analysis of the glutamate system revealed that, in the acute phase of the pathology, ABA rats increased the membrane expression of GluA1 AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits together with its scaffolding protein SAP97. Recovery of body weight reduced GluN2A/2B balance together with the expression of their specific scaffolding proteins, thus suggesting persistent maladaptive neurotransmission. Taken together, AMPA and NMDA (N-methyl-D-aspartate) receptor subunit reorganization may play a role in the motivational mechanisms underlying AN.
Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats / F. Mottarlini, G. Bottan, B. Tarenzi, A. Colciago, F. Fumagalli, L. Caffino. - In: NUTRIENTS. - ISSN 2072-6643. - 12:12(2020 Nov 28).
|Titolo:||Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats|
MOTTARLINI, FRANCESCA (Primo)
BOTTAN, GIORGIA (Secondo)
FUMAGALLI, FABIO (Penultimo)
CAFFINO, LUCIA (Ultimo) (Corresponding)
|Parole Chiave:||activity-based anorexia; adolescence; female rats; glutamatergic receptors; nucleus accumbens; reward circuit|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Progetto:||Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI|
PIANO DI SOSTEGNO ALLA RICERCA 2015-2017 - LINEA 2 "DOTAZIONE ANNUALE PER ATTIVITA' ISTITUZIONALE"
Unveiling the role of the Irisin-BNDF axis in controlling muscle to brain metabolic crosstalk in anorexia nervosa
|Data di pubblicazione:||28-nov-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/nu12123661|
|Appare nelle tipologie:||01 - Articolo su periodico|