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D-cycloserine effects on COPD and depression in a murine experimental model
Uriel Heresco-Levy1,2, Jacob Haviv1, Yehezkel G Caine1
1Herzog Medical Center, Jerusalem, Israel.
Frontiers in Pharmacology
|June 16, 2025
Summary
D-cycloserine (DCS) reduced lung injury and depression-like behaviors in a mouse model of chronic obstructive pulmonary disease (COPD). These findings suggest DCS may be a novel treatment for the comorbidity of COPD and depression.
Area of Science:
- Pulmonary Medicine
- Neuroscience
- Pharmacology
Background:
- Chronic obstructive pulmonary disease (COPD) and depression share links to chronic inflammation, presenting a significant unmet clinical need.
- N-methyl-D-aspartate glutamatergic receptors (NMDAR) are implicated in lung injury and depression through proinflammatory signaling and oxidative stress.
- D-cycloserine (DCS), an NMDAR antagonist, exhibits antidepressant and anti-inflammatory properties.
Purpose of the Study:
- To investigate NMDAR downregulation as a unified molecular target for treating COPD-depression comorbidity.
- To assess the efficacy of DCS in ameliorating lung injury and depression-like behavior in a murine COPD model.
Main Methods:
- A porcine pancreatic elastase (PPE)/E. coli lipopolysaccharide (LPS) model was used to induce COPD in male BALB/c mice.
- Mice received PPE and LPS intratracheally, followed by intraperitoneal administration of vehicle or DCS (100 or 200 mg/kg).
- Depression-like behavior was assessed using the forced swim test (FST), and lung tissues were analyzed histopathologically.
Main Results:
- The COPD model exhibited increased inflammatory cell infiltration, emphysema (mean linear intercept), and FST immobility duration compared to controls.
- DCS treatment (100 mg/kg) significantly reduced immobility duration in the FST.
- DCS administration also decreased lung inflammation severity and mean linear intercept in various treatment groups.
Conclusions:
- D-cycloserine demonstrated beneficial effects in reducing lung injury and depression-like behaviors in the COPD model.
- These findings support further investigation of DCS as an innovative therapeutic agent for COPD-depression comorbidity.
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