Effect of Hyperglycemia on Major Cell Types of Cerebellum and ralative Expression of Neuregulin Isoform 2 and 3 during Diabetes

Abstract

Cerebellum is an important part of the brain, responsible for motor learning, maintenance of body’s balance and posture, orchestrating voluntary movement, fine tuning and various other cognitive functions. There are several types of cells present in cerebellum which are interconnected to each other and form neuronal circuits. Under normal conditions, in order to maintain homeostasis, cognitive and motor functioning, cerebellum is capable of repairing and regenerating the cerebellar cells. NRG-ErbB signalling pathway mechanisms drive adult neurogenesis and regeneration. It plays a very crucial role in formation of neuronal circuits and maintaining intact neural interactions. Hyperglycemia during diabetes is known to cause histopathological alterations and NRG-ErbB signalling. Quantitation of cerebellar cell population in control and hyperglycaemic condition through Haematoxylin-Eosin and fast green staining help to visualize the Purkinje cells, basket cells, stellate cells, Golgi cells, granule cells and unipolar brush cells. The gene expression of NRG2 and NRG3 was done to study the regenerative potential in rodents. Our data revealed that under the hyperglycaemic condition there was a significant decrease in the basket cells, stellate cells, Purkinje cell, Golgi cells, granule cells and unipolar brush cells (UBC). Also, the certain cells displayed distorted morphology during hyperglycemia conditions. Hyperglycemia led to the alteration in gene expression of NRG2 and NRG3 in diabetic rats that shows association with impaired regeneration, distorted morphology and loss of various neuronal cell populations. Thus, hyperglycemia distorts the morphology and causes cellular degeneration besides dampening the cellular regeneration mediated by NRG2 and NRG3 isoforms. The structure prediction is a computational method to analyse secondary and tertiary conformations of protein from sequences of amino acid residues. NRG2 and NRG3 structure prediction was performed through procurement of FASTA sequence using tools like SWISS model, phyre2 . Further validation of model selection was done by building Ramachandran plot. To perform molecular dynamic simulation, NRG2, NRG3 and ErbB4 -Gromacs was used to study molecules in different conditions