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

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. The 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, 10 mg/kg), an antidepressant drug, and COR (10 and 50 mg/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.