Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

Abstract

The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ), prior to 3-nitropropionic acid (3-NP) insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NFκB are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NFκB nuclear accumulation was also evaluated.