Effects of cerebrolysin on behavioral changes and the tryptophan-kynurenine pathway in the prefrontal cortex of male mice in the ketamine model of schizophrenia.

A peptide derived from pig brain, Cerebrolysin, reduced anxiety- and depression-like behaviors, improved spatial learning and memory, and increased locomotor activity in a mouse model of schizophrenia induced by ketamine. It lowered kynurenine levels and raised tryptophan levels in the prefrontal cortex, indicating modulation of the tryptophan/kynurenine pathway. However, Cerebrolysin did not significantly affect the inflammatory markers NLRP3 and IL-1β compared to the ketamine-only group. The findings suggest the neuroprotective effects of Cerebrolysin are linked to its action on this metabolic pathway rather than on these specific inflammatory factors.

Study at a glance

Abstract

Cerebrolysin (CBL), a peptide derived from pig brain, is recognized for its neuroprotective and anti-inflammatory properties. This research aimed to investigate the effects of CBL on anxiety- and depression-like behaviors, spatial memory, the tryptophan/kynurenine (TRP/KYN) pathway, and inflammation in the prefrontal cortex (PFC) of a mouse model for schizophrenia. Thirty-six male BALB/c mice were allocated into three experimental groups: control, ketamine (Ket) (20 mg/kg per day, i.p.), and Ket + CBL (2.5 mL/kg per day, i.p.). The open field test was used to evaluate anxiety-like behavior and locomotor activity, while the tail suspension test was used to assess depression-like behavior. Spatial memory was evaluated using the Lashley III Maze. Moreover, KYN and TRP levels were detected using an enzyme-linked immunosorbent assay. Inflammatory factors NLRP3 and IL-1β were assessed via the Western blot method. The results demonstrated that CBL administration significantly reduced anxiety-like behaviors, improved locomotor activity, decreased immobility time, and enhanced spatial learning and memory. Furthermore, CBL significantly lowered KYN levels and increased TRP levels in the PFC. Administration of Ket caused an increase in IL-1β levels. However, CBL did not significantly impact NLRP3 and IL-1β levels compared to the Ket group. These findings demonstrate the neuroprotective properties of CBL, which are likely due to its modulatory action on the TRP/KYN pathway and improvement in spatial memory, anxiety, and depression-like behaviors in schizophrenia mice.