Role of membrane cholesterol and lipid peroxidation in regulating the Na+/K+-ATPase activity in schizophrenia

Background: Na+/K+-ATPase (NKA) activity is compromised in several neuropsychiatric disorders. Oxidative stress and membrane lipid composition play important roles in regulating NKA activity. Aims: The present study was undertaken to evaluate the effects of oxidative stress-induced membrane lipid damage and membrane cholesterol composition on NKA pump activity in schizophrenia. Settings and Design: It was a hospital-based, cross-sectional, observational study in 49 cases and 51 controls for 1 year. Materials and Methods: NKA pump activity in red blood cell membrane, serum levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) adducts, and cholesterol were measured by standard spectrophotometric techniques in newly diagnosed schizophrenia patients by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria. Membrane cholesterol was analyzed by chloroform and isopropanol extraction followed by measuring the cholesterol concentration by spectrophotometric technique. Statistical Analysis and Results: Mean values for NKA pump activity, membrane cholesterol level, and serum cholesterol levels were significantly lower in the case group (P < 0.001). The activity of NKA pump was found to be directly correlated to membrane cholesterol level rather than with the serum cholesterol values. Although the NKA pump activity showed inverse relationship with the serum values of TBARS and PC products both, on multiple linear regression analysis, it was found to be significantly positively dependent on the membrane cholesterol (β = 0.268, P = 0.01) and negatively dependent on the serum TBARS (β = −0.63, P < 0.001) levels only. Conclusion: Reduced membrane cholesterol and oxidative stress-induced damage to membrane lipids play crucial roles in decreasing the NKA activity in schizophrenia. Hence, for a better prognosis and treatment, measures are required to maintain optimum levels of cholesterol in neuronal tissues along with a proper control on oxidative stress.