Exploring the impact of melatonin and omega-3, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with dorsal CA1 hippocampal lesions

Background and objective: Damage to the hippocampus leads to increased anxiety, memory problems, and learning disabilities. Melatonin (MLT), a hormone secreted by the pineal gland, serves as an antioxidant and provides defense against nerve damage. Omega-3 (omega 3) is known for improving brain function. This study aims to examine the impact of melatonin and omega-3, both individually and in combination, on cognitive function, histological changes, and the balance between oxidants and antioxidants in male rats with injuries to the dorsal CA1 hippocampus. Material and Methods: Five rat groups (n = 8) were examined. The sham group was given normal saline via intraperitoneal (ip) and gavage routes. After a local lesion in the hippocampus, the lesion group underwent the same treatment. The MLT group was given melatonin (10 mg/kg, ip), the omega 3 group was provided with omega-3 (0.8 g/kg, gavage), and the MLT + omega 3 group received both treatments. Injections were administered every other day for 10 days. On the 11th day, behavioral assessments were conducted, and then pyramidal cells were quantified using image analysis software. Serum samples were assessed for levels of oxidants and antioxidants. Results: The results from the open field test indicated a significant increase in distance moved in the Lesion + MLT + omega 3 group compared to the lesion group (P < 0.05). Performance in the novel object recognition test showed improvement in the omega 3 and MLT + omega 3 treated groups compared to the lesion group (P < 0.05). Additionally, social interaction duration notably increased in the omega 3, MLT, and MLT + omega 3 treated groups compared to the lesion group. The number of degenerated cells in the CA1, CA2, and CA3 areas of the lesion group significantly increased compared to the sham group, but melatonin and omega-3 notably reduced this number (P < 0.05). The serum levels of the antioxidant enzymes, include superoxide dismutase, glutathione peroxidase, and catalase in the lesion group notably changed compared to the sham group, but omega-3 effectively restored them to control levels. Conclusion: According to increase in distance moved, memory function, learning and social interactions of the animal in the behavioral results and the reduction of degenerate cells in the histological results, it can be said that these effects may be part of the neuroprotective effects of melatonin and omega-3. The increase in levels of antioxidant enzymes, particularly omega-3, indicates their promise as therapeutic agents for reducing oxidative stress-induced damage in neurological disorders.