Effect of Hyperglycemia on Neurexin Mediated Synaptic Vesicle Transmission in the Cerebral Cortex of Diabetic Rats

Abstract

Neurexins are a family of transmembrane proteins, a synaptic cell adhesion molecule. It is the presynaptic cell adhesion molecule that binds to its binding partner Neuroligin, a postsynaptic cell adhesion molecule. NRXNs and NLGs connect the presynaptic and postsynaptic neurons at the synapses. This helps facilitate signaling through the synapse, where the neurotransmitters can pass from the presynaptic to the postsynaptic neuron. This can occur efficiently only when the synapse is stabilized. Diabetes mellitus is a disorder where the normal blood sugar (glucose) levels are altered than the normal and enough insulin is not present that can convert glucose to energy. It can occur if the body is unable to produce sufficient insulin, or when it cannot respond to insulin, or when the insulin is not working efficiently. Hyperglycaemia is a condition where blood glucose levels are higher than the normal levels and insulin cannot work efficiently to help the cells take in glucose which is to be used for energy. Insulin is said to have a mandatory role in synaptic transmission. There are many insulin receptors present in the neurons, and the concentration of these insulin receptor proteins in the synapses is abundant. This project was aimed at studying the effect of hyperglycemia on the expression of the neurexin protein. Under hyperglycaemic conditions, there is an alteration in the expression of the neurexin levels, that can hamper the efficient NRXN-NLG binding. Thus, synaptic stability might be affected, which prevents neurotransmitters to pass from the presynaptic to the postsynaptic neuron properly. Thus, this communication between neural networks will also be altered. This might lead to cognitive disorders. This project was designed to examine the expression of the neurexin protein under hyperglycaemic conditions with the help of gene expression and protein expression studies. Also, this project was aimed to analyse and screen out the potential drug-like molecules (phytochemicals) found from plant sources that can interact with Neurexin. This was achieved through molecular docking studies and with the use of various in silico pharmacokinetics tools. It was found that there was a total of nine antihyperglycemic phytochemicals that could interact with Neurexin and act as its activators.