Pharmaceuticals (Aug 2022)

Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour

  • Paolo Tucci,
  • Maria Bove,
  • Vladyslav Sikora,
  • Stefania Dimonte,
  • Maria Grazia Morgese,
  • Stefania Schiavone,
  • Lorenzo Di Cesare Mannelli,
  • Carla Ghelardini,
  • Luigia Trabace

DOI
https://doi.org/10.3390/ph15091054
Journal volume & issue
Vol. 15, no. 9
p. 1054

Abstract

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Glucoraphanin (GRA) is a natural compound that has shown beneficial effects in chronic diseases and in central nervous system disorders. Moreover, GRA displayed antidepressant activity in preclinical models. We have previously demonstrated that a single intracerebroventricular administration of soluble amyloid-beta 1-42 (sAβ 1-42) in rat evokes a depressive-like phenotype by increasing immobility frequency in the forced swimming test (FST). The aim of this work was to investigate the effect of GRA in naïve and in sAβ-1-42-treated rats by using the FST. Behavioural analyses were accompanied by neurochemical and biochemical measurements in the prefrontal cortex (PFC), such as serotonin (5-HT), noradrenaline (NA), kynurenine (KYN), tryptophan (TRP), reactive oxygen species (ROS) and the transcription nuclear factor kappa B (NF-kB) levels. We reported that GRA administration in naïve rats at the dose of 50 mg/kg reduced the immobility frequency in the FST and increased 5-HT and NA levels in the PFC compared to controls. At the same dose, GRA reverted depressive-like effects of sAβ 1-42 administration, restored the 5-HT levels and reduced NF-kB, KYN and ROS levels in PFC. In conclusion, GRA rapidly reverting depressive-like behaviour, together with biochemical and neurochemical alterations, might represent a safe and natural candidate for the treatment of depression.

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