Distribution of aquaporin-4 channels in prefrontal cortex and hippocampus in MK-801-induced experimental schizophrenia model

Introduction: Aquaporin-4 (AQP-4) water channels are an important component of glymphatic (glial lymphatic) system. Functional disorders of glymphatic system and AQP-4 channels takes part in the patophysiology of neurodegenerative disease.The aim of this study describe distribution of aqp-4 channels in the prefrontal cortex and hippocampus in a mouse model of NMDA receptor blocking agent induced schizophrenia like behaviour. Materyal and Method: NMDA receptor antagonist MK-801 used to produce experimental schizophrenia model. MK-801 injections for eleven days to Balb/c mice intraperitoneally. Beginning from the sixth day of injection, spatial learning and memory of the mice (N=10-11) were tested by Morris water maze (MWM) task. Time to find the hidden platform, time spent at the target quadrant when platform removed, swimming speed was recorded by Ethovision XT. A group of mouse (N=5) was injected MK-801 for ten days and without MWM task sacrified. Hippocampus and prefrontal specimens collected from this group. Hippocampus and prefrontal cortex stained immunohistochemically and AQP-4 channels examined. Tissue samples also examined by electron miroscope. Statistical analysis of behaviour tests done by repeated measure ANOVA and immunohistochemical data analysis done by Mann Whitney-U test. Results:Time to find the platform was significantly longer at MK-801 injected group than the control group at Morris water maze task. Also the time spent at the target quadrant by MK-801 group was shorter compared to control group (p<0,001). Immunohistochemically AQP-4 expression increased significantly at hippocampal glial cells, perineuronal (p<0,01) and pericapillary (p<0,0001) spaces. At the prefrontal cortex AQP-4 expression at the glial cells (p<0,01) and precapillary space (p<0,001) is increased, perineuronal space there is tendency to increase. Electron microscobically glial cells and neurons at the hippocampus and prefrontal cotex of the MK-801 study group there is increased nuclear chromatin, cytoplasmic organel destruction detected. Eudema at the pericapillary space is seen. Increased AQP-4 channel expression and neurodegeneration at the prefrontal cortex and hippocampus at the MK-801 induced schizophenia-like behaviour model. Conclusion: MK-801 induced NMDA receptor blockade causes decline in the cognitive and memory functions. Increased AQP-4 expression at the prefrontal cortex and hippocampus in order to elicit and transport products of synaptic neurotransmitters and end metabolites is suggested.