Extreme Glycemic Fluctuations Debilitate NRG1, ErbB Receptors and Olig1 Function: Association with Regeneration, Cognition and Mood Alterations During Diabetes

Abstract

Neuronal regeneration is crucial for maintaining intact neural interactions for perpetuation of cognitive and emotional functioning. The NRG1-ErbB receptor signaling is a key pathway for regeneration in adult brain and also associated with learning and mood stabilization by modulating synaptic transmission. Extreme glycemic stress is known to affect NRG1-ErbB-mediated regeneration in brain; yet, it remains unclear how the ErbB receptor subtypes are differentially affected due to such metabolic variations. Here, we assessed the alterations in NRG1, ErbB receptor subtypes to study the regenerative potential, both in rodents as well as in neuronal and glial cell models of hyperglycemia and hypoglycemic insults during hyperglycemia. The pro-oxidant and anti-oxidant status leading to degenerative changes in brain regions were determined. The spatial memory and anxiogenic behaviour of experimental rodents were tested using ‘T’ maze and Elevated Plus Maze. Our data revealed that the extreme glycemic discrepancies during diabetes and recurrent hypoglycemia lead to altered expression of NRG1, ErbB receptor subtypes, Syntaxin1 and Olig1 that shows association with impaired regeneration, synaptic dysfunction, demyelination, cognitive deficits and anxiety.