Reduced Efr3a Promotes Neurogenesis in the Hippocampus

The brain generates new cells at a fairly sedate pace in the process known as neurogenesis, slowly integrating newly created cells into existing neural circuits. This enables some modest degree of repair of damage, but also appears to be important in the normal operation of the mind. Modestly increased levels of neurogenesis in the brain so far seem to be wholly beneficial when examined in animal studies. Unfortunately the pace of neurogenesis slows with age, so there is some interest in the research community in finding ways to boost the process, either with or without addressing its causes. A general method of enhancing neurogenesis would probably be beneficial for cognitive function at any age, if the animal data is any guide.

New research sheds important light on the inner workings of learning and memory. Specifically, scientists show that a plasma membrane protein, called Efr3, regulates brain-derived neurotrophic factor (BDNF) / tropomyosin-related kinase B (TrkB) signaling pathway and affects the generation of new neurons in the hippocampus of adult brains. In turn, this generation of new neurons plays a significant role in learning and memory. "Our study demonstrates that Efr3a is associated with BDNF signaling and adult neurogenesis, which are important for learning and memory. We hope our results will provide new insights into the mechanisms underlying learning and memory."

To draw their conclusions, the researchers crossbred genetically altered mouse strains to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. Brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Also, the BDNF-TrkB signaling pathway was enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF-TrkB, and the downstream molecules, including phospho-MAPK (mitogen-activated protein kinase) and phospho-Akt. "This study once again emphasizes the extreme importance of neurogenesis specifically linked to neurotrophic signaling in the hippocampus. We are again reminded of how far we have come from the era in which neurogenesis in the adult mammalian brain was not believed to even occur."