Antidepressant effects of C-Terminal domain of the heavy chain of tetanus toxin in a rat model of depression

Bruk Getachew, Liliana Mendieta, Antonei B. Csoka, José Aguilera, Yousef Tizabi

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Abstract

The C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) may be of therapeutic potential in motor impairments associated with Parkinson disease (PD). Since depression is a common co-morbid condition with PD, we undertook this study to determine whether Hc-TeTx might also show antidepressant-like properties and whether central brain-derived neurotrophic factor (BDNF) and/or tumor necrosis factor (TNF)-alpha are also affected by it. Adult male Wistar-Kyoto rats, a putative animal model of depression, were treated with various doses of Hc-TeTx (0, 20, 40 and 60 mu g/kg, IM) and their performance in the open field locomotor activity (OFLA) as well as in the forced swim test (FST) was evaluated at 24 h, one week and two weeks after the single injection. A separate group of rats were injected with 60 mu g/kg Hc-TeTx and sacrificed 24 h later for neurochemical evaluations. Hc-TeTx resulted in a dose-dependent decrease in immobility score after 24 h, whereas OFLA was not affected. Concomitant with the 24 h behavioral effects, the levels of hippocampal and frontal cortical BDNF were significantly increased, whereas the levels of TNF-alpha in both these areas were significantly decreased. The decrease in immobility scores following higher doses of Hc-TeTx were still evident after one week, but not 2 weeks of rest. These results indicate long lasting antidepressant effects of a single Hc-TeTx dose and suggest potential utility of Hc-TeTx in PD-depression co-morbidity.

Original languageEnglish
Article number111968
Pages (from-to)111968
Number of pages5
JournalBehavioural Brain Research
Volume370
DOIs
Publication statusPublished - 16 Sep 2019

Keywords

  • BDNF
  • FRAGMENT
  • Forced swim test
  • Frontal cortex
  • Helplessness
  • Hippocampus
  • IMPROVES
  • INTRAMUSCULAR INJECTION
  • MOTOR BEHAVIOR
  • Parkinson's disease
  • TNF-alpha

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    Getachew, B., Mendieta, L., Csoka, A. B., Aguilera, J., & Tizabi, Y. (2019). Antidepressant effects of C-Terminal domain of the heavy chain of tetanus toxin in a rat model of depression. Behavioural Brain Research, 370, 111968. [111968]. https://doi.org/10.1016/j.bbr.2019.111968