Abstract
Background:
Major depressive disorder (MDD) is one of the leading causes of disability aworldwide (Kessler et al., 2003). Despite rapid-acting antidepressants ketamine elicits rapid and sustained antidepressant effects, chronic use causes side effects like addiction or hallucinogenic(Smith-Apeldoorn et al., 2022). Emerging clinical studies have demonstrated the rapid onset of antidepressant effects of single-bout physical exercise (Brush et al., 2021, Ge et al., 2021). However, the neural mechanisms underlying this action have not been identified.
Aims & objectives
We investigated whether enhanced glutamatergic activity in the frontal cortex underlying rapid antidepressant action of single bout of physical exercise in a mouse model of chronic unpredictable stress.
Method
We used Cre-CAMKII transgenic mice and two-photon calcium imaging to examine involvement of glutamatergic neurons in the frontal cortex in the rapid antidepressant effects of a 30-min high intensity treadmill training. Behavioral despair was assessed by forced swim test, tail suspension test and splash test 2-hr post exercise. Neural activation was examined by quantifying c-Fos positive cells in different brain regions. Chemogenetic activation and inhibition of glutamatergic neurons were examined respectively in mice with single bout of treadmill training.
Results
Our pilot data have shown that single bout of physical exercise elicited a rapid (30 min post-exercise) and sustained antidepressant effect (last to 24 hours post-exercise). Whole brain c-fos mapping indicated that anterior cingular cortex (ACC) could be a key brain region mediating the rapid onset of antidepressant effect of single bout of exercise, as evidenced by significant increase in c-Fos positive cells when compared to non-exercised control Co-labeling has identified glutamatergic neurons as the major neuronal type responding to the exercise training. Acute chemogenetic activation of glutamatergic neurons in the ACC mimicked the effects of exercise whereas inhibition of glutamatergic neurons abolished the rapid antidepressant effects of exercise.
Discussion and conclusion
This study has suggested the critical role of ACC-glutamatergic neurons in rapid antidepressant induced by single bout of exercise.
Major depressive disorder (MDD) is one of the leading causes of disability aworldwide (Kessler et al., 2003). Despite rapid-acting antidepressants ketamine elicits rapid and sustained antidepressant effects, chronic use causes side effects like addiction or hallucinogenic(Smith-Apeldoorn et al., 2022). Emerging clinical studies have demonstrated the rapid onset of antidepressant effects of single-bout physical exercise (Brush et al., 2021, Ge et al., 2021). However, the neural mechanisms underlying this action have not been identified.
Aims & objectives
We investigated whether enhanced glutamatergic activity in the frontal cortex underlying rapid antidepressant action of single bout of physical exercise in a mouse model of chronic unpredictable stress.
Method
We used Cre-CAMKII transgenic mice and two-photon calcium imaging to examine involvement of glutamatergic neurons in the frontal cortex in the rapid antidepressant effects of a 30-min high intensity treadmill training. Behavioral despair was assessed by forced swim test, tail suspension test and splash test 2-hr post exercise. Neural activation was examined by quantifying c-Fos positive cells in different brain regions. Chemogenetic activation and inhibition of glutamatergic neurons were examined respectively in mice with single bout of treadmill training.
Results
Our pilot data have shown that single bout of physical exercise elicited a rapid (30 min post-exercise) and sustained antidepressant effect (last to 24 hours post-exercise). Whole brain c-fos mapping indicated that anterior cingular cortex (ACC) could be a key brain region mediating the rapid onset of antidepressant effect of single bout of exercise, as evidenced by significant increase in c-Fos positive cells when compared to non-exercised control Co-labeling has identified glutamatergic neurons as the major neuronal type responding to the exercise training. Acute chemogenetic activation of glutamatergic neurons in the ACC mimicked the effects of exercise whereas inhibition of glutamatergic neurons abolished the rapid antidepressant effects of exercise.
Discussion and conclusion
This study has suggested the critical role of ACC-glutamatergic neurons in rapid antidepressant induced by single bout of exercise.
| Original language | English |
|---|---|
| Publication status | Published - May 2024 |
| Event | The 25th World Congress Collegium Internationale Neuro-psychopharmaacologi - Japan, Tokyo, Japan Duration: 23 May 2024 → 26 May 2024 https://cinp2024.org/academic-program/ |
Congress
| Congress | The 25th World Congress Collegium Internationale Neuro-psychopharmaacologi |
|---|---|
| Abbreviated title | CINP |
| Country/Territory | Japan |
| City | Tokyo |
| Period | 23/05/24 → 26/05/24 |
| Internet address |