Objective
To investigate the antagonistic effect of ω-3PUFAs on cognitive impairment in MK-801-induced schizophrenia (SZ) rats and its mechanism.
Methods
Rat model of schizophrenia was induced by MK-801. Morris water maze was used to detect the change of cognitive function in rats. The number of neonatal neurons in hippocampus was detected by Brdu staining. CREB, p-CREB, BDNF, TrkB and p-TrkB levels were detected by Weston Blot.
Results
MK-801 induced schizophrenia-like cognitive impairment (the escape latency in the water maze test was (6.51±3.10)s for Ctr group, (15.27±6.20)s for Mod group; acrossing times was (4.63±1.06) times for Ctr group, (2.00±1.15) times for Mod group), reduced the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area, Mod/Ctr was 0.656±0.066) and impaired the CREB/BDNF/TrkB pathway (the relative level of gray value, Mod/Ctr: CREB was 0.393±0.065, p-CREB was 0.591±0.015, BDNF was 0.716±0.115, TrkB was 0.787±0.029, p-TrkB was 0.586±0.013). ω-3PUFAs improved the CREB/BDNF/TrkB pathway activity by increasing CREB and TrKB level and their phosphorylation (the relative level of gray value, Pre/Ctr: CREB was 1.139±0.111, p-CREB was 0.845±0.243, BDNF was 0.864±0.133, TrkB was 0.916±0.022, p-TrkB was 0.952±0.047), and then recovered the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area, Pre/ Ctr was 1.183±0.101), thereby reduced the cognitive dysfunction in schizophrenia rats(the escape latency in the water maze was (7.44±4.55)s for Pre; acrossing times was (3.86±1.68) times for Pre).
Conclusion
ω-3PUFAs can relieve the MK-801-induced schizophrenia-like cognitive impairment.
Key words:
Schizophrenia; MK-801; ω-3PUFAs; Cognition impairment