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TRPA1 participation in behavioral impairment induced by chronic corticosterone administration
Gabriele Cheiran Pereira1,2, Elisa Piton1, Jéssica Bornholdt1
1Center of Health Sciences, Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Rationale:
Major depressive disorder (MDD) is one of the most diagnosed mental disorders. Despite this, its pathophysiology remains poorly understood. In this context, basic research aims to unravel the pathophysiological mechanisms of MDD as well as investigate new targets and substances with therapeutic potential. Transient receptor potential ankyrin 1 (TRPA1) is a transmembrane channel considered a sensor for inflammation and oxidative stress. Importantly, both inflammation and oxidative stress have been suggested as participants in the pathophysiology of MDD. However, the potential participation of TRPA1 in depressive disorder remains poorly investigated.
Objective:
To investigate the involvement of the TRPA1 channel in the behavioral changes induced by chronic corticosterone administration (CCA) in male mice.
Methods:
Swiss male mice were exposed to 21 days of CCA protocol and then treated with HC-030031 or A-967079, TRPA1 antagonists. Behavioral tests, analyzes of oxidative parameters and TRPA1 immunocontent were performed in the prefrontal cortex (PFC) and hippocampus (HIP).
Results:
CCA induced despair-like behavior in mice accompanied by an increase in the levels of hydrogen peroxide (H2O2), a TRPA1 agonist, which was reversed by TRPA1 antagonists and ketamine (positive control). In addition, CCA protocol reduced the immunocontent of this channel in the HIP and showed a tendency to increase the TRPA1 protein expression in the PFC.
Conclusion:
Our work suggests that TRPA1 channel appears crucial to mediate the behavioral impairment induced by CCA in male Swiss mice.
Insights
The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is implicated in the behavioral changes of major depressive disorder (MDD) in mice. Blocking TRPA1 reversed depression-like behaviors and oxidative stress markers.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Major depressive disorder (MDD) pathophysiology is not fully understood, yet inflammation and oxidative stress are implicated.
- The Transient Receptor Potential Ankyrin 1 (TRPA1) channel, a sensor for oxidative stress and inflammation, has not been extensively studied in relation to MDD.
- Investigating novel therapeutic targets for MDD is crucial given its high prevalence.
Purpose of the Study:
- To explore the role of the TRPA1 channel in the behavioral alterations associated with chronic corticosterone administration (CCA) in male mice.
- To determine if TRPA1 antagonists can mitigate CCA-induced behavioral changes and associated molecular markers.
Main Methods:
- Male Swiss mice underwent a 21-day chronic corticosterone administration (CCA) protocol.
- Mice were treated with TRPA1 antagonists (HC-030031 or A-967079) or ketamine (positive control).
- Behavioral tests, oxidative stress parameters (H2O2), and TRPA1 immunocontent were assessed in the prefrontal cortex (PFC) and hippocampus (HIP).
Main Results:
- CCA induced despair-like behaviors and increased hydrogen peroxide (H2O2) levels, a TRPA1 agonist.
- TRPA1 antagonists and ketamine reversed these CCA-induced behavioral deficits and oxidative stress.
- CCA altered TRPA1 immunocontent in the hippocampus and prefrontal cortex.
Conclusions:
- The TRPA1 channel plays a significant role in mediating the behavioral impairments induced by chronic corticosterone administration in male mice.
- TRPA1 antagonism presents a potential therapeutic strategy for depression-related behavioral changes linked to oxidative stress.
