Enhanced neurogenesis in degenerated hippocampi following pretreatment with miR-302/367 expressing lentiviral vector in mice

Abstract

Astrogliosis is the main landmark of neurodegenerative diseases. In vivo reprogramming of reactive astrocytes to functional neurons opened a new horizon in regenerative medicine. However there is little evidence that show possible application of in vivo reprogramming approaches for enhancement of neurogenesis. Cluster miR-302/367 showed high capability in cell reprogramming. Here we show that application of lentiviral particles expressing cluster miR-302/367 along with systemic valproate (VPA) enhanced the capability of mice brains for neurogenesis in CA3 area following kainic acid (KA) induced hippocampal neurodegeneration. Following pretreatment with miR-302/367 expressing viral particles and VPA, transduced cells showed neuroblast and mature neuron markers when neuronal loss was induced by KA. Comparing the neuron counts in CA3 region also showed that neurogenesis was increased in CA3 region in animals which were pretreated with miR-302/367 vector and VPA, only in injected side of the brain. Our data suggest that targeted application of miR-302/367 expressing vector may enhance the capacity of hippocampus and other brain structures for regeneration following neuronal loss.