Effect of Hypoglycemia on type III Neuregulin-1 Gene Expression and Lactate Dehydrogenase in Streptozotocin Induced Diabetic Rats.

Abstract

Brain is dependent on a continual supply of glucose diffusing from the blood. Hence low amount of blood glucose affect the brain first. Subtle reduction of cognitive efficiency is one of common side effect of hypoglycaemia can be observed when the glucose falls below 65 mg/dl. So Glucose homeostasis in humans is a critical factor for the functioning of nervous system. Hypoglycemia, diabetic hypoglycemia and hyperglycemia are found to be associated with central and peripheral nerve system dysfunction. Hyperglycemia and hypoglycaemia induces oxidative stress in neurons and results in activation of multiple biochemical pathways. These activated pathways are a major source of damage and are potential therapeutic targets in neuropathy. NRG-1 found both as in membrane-anchored regions and also as soluble form work as a cytokine that binds to their erbB2 receptor and activate to appropriate downstream signaling cascade and made a protein product that regulates developmental neuronal survival synaptogenesis, astrocytic differentiation, and microglial activation. Neuronal over expression of NRG-1 induces hypermyelination and demonstrates that NRG-1 type III is the responsible isoform. We carried out experiments to investigate the role of diabetes and insulin induced hypoglycemia by performing behaviour analysis test for the assessment of motor activity (Grid Walking test), cognition (Modified Karl Lashley’s Maze) and anxiety (Elevated Plus maze). Lactate dehydrogenase (LDH) was used as a marker enzyme to study the gluconeogenic pathway. LDH is also involved in gluconeogenesis, the synthesis of glucose from smaller molecules and also catalyzes the conversion of lactate to pyruvate utilizing the NAD/NADH coenzyme system. Cellular oxidative damage (i.e. Lipid peroxidation) by Peroxidative damage to lipids was determined by measuring Malondialdehyde concentration in Liver by performing Thio Barbituric Acid Reactive Substance enzyme assay spectrophotometrically at 532 nm. Lipid peroxidation was significantly enhanced in Diabetic + insulin induced hypoglycaemic (D+IIH), Control+ insulin induced Hypoglycemia (C+IIH), and Diabetes (D) groups When compared to Control. The increase of reactive oxygen species levels can be because of neurochemical alterations during seizures in hypoglycemia groups