Effect of Alpha and Beta Adrenergic Receptors on the Expression of Stk4, Caspase-3, and Sox2 Genes in Neural Stem Cells Derived From the Hippocampus and Treated With Norepinephrine in Rats

Abstract

Background and Objectives Uncontrolled stress affects hippocampal-dependent memory through altering the morphology and the proliferation rate of hippocampal progenitor cells. Subjects and Methods In this experimental study, neural stem cells (NSCs) were isolated from the hippocampus of newborn rats and cultivated in a serum-free medium to generate neurosphere. To confirm the induced NSCs, immunocytochemistry and antibody nestin were used. The rate of cell proliferation and cytotoxicity caused by norepinephrine were measured by the MTT assay. NSCs were assigned in the following groups: Control (untreated NSCs), norepinephrine (NSCs treated with norepinephrine), propranolol (NSCs treated with beta receptor blocker propranolol plus norepinephrine), prazosin (NSCs treated with Alfa receptor blocker prazosin plus norepinephrine), and propranolol/ prazosin (NSCs treated with both propranolol and prazosin plus norepinephrine). Real-time PCR was conducted to measure the expression levels of Stk4, Caspase-3 and Sox2 genes. Results The flow cytometry study revealed that NSCs were nestin positive. Real-time PCR results showed that the expression level of Sox2 gene increased by norepinephrine. In addition, the expression level of Stk4 and Caspase-3 genes increased in the groups treated with prazosin. Conclusion The effect of norepinephrine on hippocampus-derived NSCs is receptor-dependent. The increase of norepinephrine under chronic stress can lead to either cell proliferation or apoptosis in NSCs; it acts as a double-edged sword.