BDNF-TrkBsignallingin nucleus accumbens shell isimplicated in perinatal protein malnutrition-induced anhedonia

PERONDI MC; GUTIERREZ MC; VALDOMERO A; CUADRA GR

Congreso; XXXV Annual (Virtual) Meeting SAN 2020; 2020

Clinical studies have suggested that early malnutrition increases the risk of developing depressive disordersin adulthood. The molecular mechanisms underlying depression have been studied for decades, however many of themremain unknown.Previous results from our lab have shownthat perinatal protein undernutrition-induced anhedoniacorrelates with an increment in the levels of brain derived neurotrophic factor (BDNF) in the nucleus accumbens (NAc).Here, we evaluatethe high affinity receptor of BDNF (TrkB) and its phosphorylated form (p-TrkB) levelsin the NAc of adult animals submitted to a perinatal protein deprivation schedule (D-rats) and well-nourished animals (C-rats) after sucrose preference test.Toconfirm whether BDNF-TrkB signaling pathway is involved in the onset of anhedonia,we administered intra-NAc shell ANA 12,a selective antagonist of TrkB.The results showed a significantly higher p-TrkB/TrkB ratio in the NAc of D-rats compared to C-group. Furthermore, D-animals infused with vehicle exhibiteda significant reduction of sucrose preference in relation to C-rats. Bilateral infusion of ANA-12 reverses such depression-like behaviour promoting an antidepressant effect. These resultssuggest a key role of BDNF-TrkB signalling in the NAc shell in the neurobiological mechanism underlyingbehavioural abnormality demonstrated in undernourished animals.