An acute hyperglycemia or acidosis-induced changes of indolamines level correlates with PKC-α expression in rat brain

Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal's results in altered brain neurotransmitter levels. In this study, we investigated the effects of acute (7 days) glucose-induced hyperglycemia and sodium acetoacetate (NaAcAc) or ammonium chloride (NH4Cl) induced acidosis on the level of indolamines (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)) as well as PKC-α expression/activity in discrete areas of rat brain. Glucose-induced (500 mg/kg, bw) hyperglycemic (∼249 mg%) rats showed significant (p < 0.05) increase in 5-HT levels in mid brain (MB), pons medulla (PM) and cerebellum (CB), respectively. 5-HIAA level increased in hippocampus (HC) (p < 0.05) as compared to control. The rats treated with sodium acetoacetate (NaAcAc) for 7 days (60 mg/kg, bw) showed significant decrease (p < 0.05) of 5-HT level in hypothalamus (HT). Whereas, the 5-HIAA level increased in MB (p < 0.05). Similarly, the PKC-α expression as well as the enzyme activity showed significant increase in HC, MB, PM and CB under glucose-induced hyperglycemia and that changes correlated the changes of indolamines, suggesting that the hyperglycemia may be the major metabolic disorder in diabetic complications.