Cognitive and Anti-inflammatory Effects of Palmaria palmata in a Schizophrenia Mouse Model: Insights into CREB and Iba-1 Expression, and CD4+ Cell Modulation

Shimaa Yousof^1*Badrah Saeed Alghamdi^1*Thamer Alqurashi¹Mohammad Zubair Alam¹Reham Tash¹Noha Mohamed Abd Elfadeal²Samy A. Abusikkien¹Lamis Kaddam¹

• ¹King Abdulaziz University, Jeddah, Saudi Arabia
• ²Suez Canal University, Ismaïlia, Ismailia, Egypt

Background: Schizophrenia is a prevalent mental illness characterized by complex behavioral and emotional challenges, with its underlying molecular mechanisms still to be elucidated. Aim: To examine the neuroprotective properties of Palmaria palmata (Palmaria p.) in relation to cognitive function in the Schizophrenia model. Methods: The study involved 28 adult male SWR Swiss mice (Duration 30 days). Animals were randomly assigned into four groups (n=7): Control, Cuprizone (CPZ) (0.2% CPZ in chow), CPZ + Palmaria p. (600 µg/kg bw/day by gavage), and Palmaria p. only group. Antioxidant activity of Palmaria p. was assessed using radical scavenging assay. Behavioral changes, hippocampal (HC) and frontal cortex (FC) gene expression, and histopathological alterations were assessed. Results: Palmaria p. demonstrated remarkable antioxidant capability induced by CPZ. No substantial impacts were seen in spatial memory, NORT and anxiety-related behaviors. In the CPZ-treated group, Iba1 and CREB expression increased in the HC and FC. In the CPZ + Palmaria p. group, Iba1 expression decreased ~1-fold in the HC and ~2-fold in the FC, while CREB expression was decreased ~2-fold in both regions compared to CPZ alone, suggesting mitigation of neuroinflammation and restoration of neuroplasticity. The immunohistochemistry revealed a notable decline in CD4 positivity if Palmaria p. was administered, suggesting a decrease in the immunological response generated by CPZ. Conclusion: The results highlight the potential of Palmaria p. for enhancing neuroplasticity and mitigating neuronal inflammation linked to schizophrenia.