Activity-Based Anorexia Dynamically Dysregulates the Glutamatergic Synapse in the Nucleus Accumbens of Female Adolescent Rats.
Francesca MottarliniGiorgia BottanBenedetta TarenziAlessandra ColciagoFabio FumagalliLucia CaffinoPublished in: Nutrients (2020)
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.
Keyphrases
- transcription factor
- physical activity
- body weight
- binding protein
- poor prognosis
- anorexia nervosa
- weight loss
- end stage renal disease
- ejection fraction
- body mass index
- newly diagnosed
- young adults
- chronic kidney disease
- mental health
- bariatric surgery
- arabidopsis thaliana
- roux en y gastric bypass
- case report
- peritoneal dialysis
- long non coding rna
- clinical trial
- prognostic factors
- type diabetes
- gastric bypass
- skeletal muscle
- atomic force microscopy
- single molecule
- study protocol