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

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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.

No MeSH data available.


tBHQ pretreatment preventive effect on motor changes induced by 3-NP. Parameters of motor activity were determined as described in Section 2. A. Percentage of horizontal movements determined for adult and old rats. B. Percentage of vertical movements determined for adult and old rats. C. Percentage of total distance walked determined for adult and old rats. Black circles represent the number of independent experiments carried out in each treatment in both groups of animals (n=3–5) and represent the mean±SD. The significance level for adult animals is expressed as follows: Adult ap<0.01 vs Ct, bp<0.01 vs tBHQ and the old animals ap<0.05 vs 3-NP, bp<0.05 vs Ct, cp<0.05 vs 3-NP.
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f0010: tBHQ pretreatment preventive effect on motor changes induced by 3-NP. Parameters of motor activity were determined as described in Section 2. A. Percentage of horizontal movements determined for adult and old rats. B. Percentage of vertical movements determined for adult and old rats. C. Percentage of total distance walked determined for adult and old rats. Black circles represent the number of independent experiments carried out in each treatment in both groups of animals (n=3–5) and represent the mean±SD. The significance level for adult animals is expressed as follows: Adult ap<0.01 vs Ct, bp<0.01 vs tBHQ and the old animals ap<0.05 vs 3-NP, bp<0.05 vs Ct, cp<0.05 vs 3-NP.

Mentions: Under our experimental conditions (Fig. 1), when the adult rats were treated with 3-NP, an hypoactive effect was observed, evidenced by a decrease in the number of vertical movements (VM) and in the TDW (p<0.05), representing the hypokinetic activity which is observed in late stages of Huntington's disease (HD) (Fig. 2B and C); on the contrary, animals treated with tBHQ showed an hyperactive pattern in the total distance walked (TDW) (p<0.05) (Fig. 2C). Old rats improved horizontal movements (HM) (Fig. 2A) and VM (Fig. 2B) with tBHQ pre-treatment (PreT) (p<0.05), compared with animals that were treated only with 3-NP and which showed a prominent VM hypoactive pattern (p<0.05). The Versamax Accuscan device employed here can record horizontal, vertical and ambulatory activities, displays maps of trajectories and also offers parameters such as total time in movement, total resting time, tome spent in the center and stereotypies. Thus, we presented in this manuscript only those parameters showing changes or minimally important trends. No changes in stereotypies were found. The method used here is simple, but represents a real spontaneous activity measure, specially considering that the possible artefactual variables -such as fear and/or anxiety- were considerably reduced and strictly controlled prior to the assay.


Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid
tBHQ pretreatment preventive effect on motor changes induced by 3-NP. Parameters of motor activity were determined as described in Section 2. A. Percentage of horizontal movements determined for adult and old rats. B. Percentage of vertical movements determined for adult and old rats. C. Percentage of total distance walked determined for adult and old rats. Black circles represent the number of independent experiments carried out in each treatment in both groups of animals (n=3–5) and represent the mean±SD. The significance level for adult animals is expressed as follows: Adult ap<0.01 vs Ct, bp<0.01 vs tBHQ and the old animals ap<0.05 vs 3-NP, bp<0.05 vs Ct, cp<0.05 vs 3-NP.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5384325&req=5

f0010: tBHQ pretreatment preventive effect on motor changes induced by 3-NP. Parameters of motor activity were determined as described in Section 2. A. Percentage of horizontal movements determined for adult and old rats. B. Percentage of vertical movements determined for adult and old rats. C. Percentage of total distance walked determined for adult and old rats. Black circles represent the number of independent experiments carried out in each treatment in both groups of animals (n=3–5) and represent the mean±SD. The significance level for adult animals is expressed as follows: Adult ap<0.01 vs Ct, bp<0.01 vs tBHQ and the old animals ap<0.05 vs 3-NP, bp<0.05 vs Ct, cp<0.05 vs 3-NP.
Mentions: Under our experimental conditions (Fig. 1), when the adult rats were treated with 3-NP, an hypoactive effect was observed, evidenced by a decrease in the number of vertical movements (VM) and in the TDW (p<0.05), representing the hypokinetic activity which is observed in late stages of Huntington's disease (HD) (Fig. 2B and C); on the contrary, animals treated with tBHQ showed an hyperactive pattern in the total distance walked (TDW) (p<0.05) (Fig. 2C). Old rats improved horizontal movements (HM) (Fig. 2A) and VM (Fig. 2B) with tBHQ pre-treatment (PreT) (p<0.05), compared with animals that were treated only with 3-NP and which showed a prominent VM hypoactive pattern (p<0.05). The Versamax Accuscan device employed here can record horizontal, vertical and ambulatory activities, displays maps of trajectories and also offers parameters such as total time in movement, total resting time, tome spent in the center and stereotypies. Thus, we presented in this manuscript only those parameters showing changes or minimally important trends. No changes in stereotypies were found. The method used here is simple, but represents a real spontaneous activity measure, specially considering that the possible artefactual variables -such as fear and/or anxiety- were considerably reduced and strictly controlled prior to the assay.

View Article: PubMed Central - PubMed

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 NF&kappa;B are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NF&kappa;B nuclear accumulation was also evaluated.

No MeSH data available.