What does this research mean for the field?

Cordycepin improves PTSD-like symptoms in mice by normalizing HPA axis function and reducing neuroinflammation. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

The study investigates the neuroprotective effects of cordycepin on PTSD-like behaviors in a mouse model exposed to early life stress.

March 7, 2026Open Access

Exploiting the behavioural and biochemical effects of cordycepin in PTSD-like behaviour using an early life stress mouse model

Key Points

The study investigates the neuroprotective effects of cordycepin on PTSD-like behaviors in a mouse model exposed to early life stress.
Swiss albino mice were subjected to sequential stressors during their first 30 days.
Mice displaying PTSD-like symptoms received treatments of fluoxetine or cordycepin.
Four behavioral tests evaluated symptom clusters comparable to human PTSD.
Immunoassays measured cortisol and neuroinflammatory markers in serum and brain tissue.
Mice developed PTSD-like symptoms alongside elevated brain cytokines IL-6, TNF-α, and NLRP3 levels.
Treatment with fluoxetine reduced all four PTSD symptom clusters.
Cordycepin showed a dose-dependent improvement in behavioral and biochemical measures.
The 50 mg/kg dose of cordycepin notably normalized HPA axis function and reduced inflammation.

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating neuropsychiatric condition triggered and precipitated by exposure to severe, life-threatening trauma. Emerging evidence implicates the involvement of neuroinflammatory processes in the exacerbation and progression of PTSD. Cordycepin (COR), a natural compound, is reported to alleviate neuroinflammation via downregulating NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes. Present study aimed to extrapolate the neuroprotective mechanism of COR against PTSD in mice. Swiss albino mice experienced PTSD-like symptoms due to sequential stressors in first 30 days at critical intervals. Mice exhibiting PTSD-like behaviour were treated with fluoxetine (FLU, 10mg/kg), an antidepressant drug, and COR (10 and 50mg/kg). Four behavioural tests were performed in mice to assess the four symptom clusters similar to human PTSD. At the end of the study, immunoassays were performed for serum corticotropin releasing hormone (CRH) and corticosterone (CORT) levels as well as brain neuroinflammation markers including interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interleukin-1β (IL-1β) and NLRP3. Behavioural assays demonstrated PTSD-like clusters in mice as observed in clinics. These cluster were associated with elevated levels of brain cytokines IL-6, TNF-α, IL-1β and NLRP3. Dysregulation of hypothalamus-pituitary-adrenal (HPA) axis was evident from significant decline in CORT levels. FLU significantly attenuated the four clusters of PTSD with negative effect on brain cytokines. COR demonstrated a dose-dependent response with 50 mg/kg showing consistent improvement in both behavioural and biochemical parameters. Overall, COR exhibited promising activity in this model and may serve as a potential natural therapeutic strategy to investigate for the management of PTSD in clinics. • Mice exposed to combination of stressors developed PTSD-like symptom clusters. • HPA axis dysregulation, elevation in cytokines and NLRP3 inflammasomes were noted • Animals treated with cordycepin showed improvement in the PTSD-like symptoms • Cordycepin normalised HPA function by resuming normal CORT levels • Significantly reduced NLRP3 protein levels along with a reduction in brain cytokines

Exploiting the behavioural and biochemical effects of cordycepin in PTSD-like behaviour using an early life stress mouse model

Key Points

Abstract

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