Hippocampal BDNF mediated anxiety-like behaviours induced by obesogenic diet withdrawal

Obesogenic diets (ODs) consumption is associated with anxiety-like behaviour and negative changes in hippocampal BDNF. At the same time, interrupting OD intake, OD withdrawal (WTD), can bring health benefits, but previous studies reported the development of anxiety-like behaviours. The present work aimed to assess the relationship between anxiety-like behaviour with hippocampal BDNF in a WTD rodent model. Male Wistar rats (60d old) were fed a high-sugar/high-fat (HSHF) diet for 30d (n = 32), and half of them were transitioned to a control diet for 48 h (n = 16) afterwards. The control group (n = 16) was fed a control diet across the whole experiment. Besides increasing anxiety-like behaviours and lowering sociability, the WTD led to an increase in BDNF in the dentate gyrus and the CA1 of the hippocampus. It also decreased locomotor activity in both OF and EPM, however, they did not significantly interfere with the other behavioural parameters analysed. Western blotting analysis revealed that the increase in BDNF likely occurred in the mature forms (14 kD monomer and 28 kD dimer). The mediation models analyses suggested that the effect of WTD on anxiety-like behaviour was driven by hippocampal BDNF, this mediation of effect was region-dependent. Our results also suggested that mature BDNF forms (14 kD and 28 kD) were responsible. The present work brought light to a possible new role for mature BDNF, although it is generally associated with beneficial features, it can also be part of the genesis of anxiety-like behaviours and sociability aspects on WTD models.