Speaker: Henriette van Praag, Ph.D., Investigator at Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging/National Institutes of Health

Talk Summary:
Most neurons in the adult central nervous system are terminally differentiated and cannot be replaced when they die. However, research over the past two decades has shown that small populations of new neurons are generated in the mature olfactory bulb and the hippocampus. In the adult hippocampus, newly born neurons originate from putative stem cells that exist in the subgranular zone of the dentate gyrus. 

 

The production, survival and functional integration of newborn hippocampal cells can be upregulated by voluntary exercise in a running wheel in rodents. Enhanced adult hippocampal neurogenesis is correlated with increased synaptic plasticity in the dentate gyrus, improved spatial navigation and pattern separation in rodents, indicating that adult-born hippocampal cells play a role in cognition (Voss et al., 2013). 

 

These newly born neurons are an integral part of local intra-hippocampal circuits as well as more distal (sub)cortical networks. A recent focus of our research is to understand the functional contribution of the different structures that provide direct input to new neurons in the adult brain during their development, as well as the reorganization of new neuron networks by exercise (Vivar et al., 2016). 

 

Another important aspect of our research is to investigate the triggers of exercise induced changes in the brain. For these studies, we are researching the muscle-brain axis. Interestingly, compounds that activate energy metabolism pathways in muscle with AMP-kinase agonist AICAR (Narkar et al., 2008) can also benefit adult neurogenesis and memory function (Kobilo et al., 2011). 

 

Based on these concepts and findings we set out to identify factors that may be released into circulation from muscle (myokines) that influence brain function. Using proteomic analysis, we found elevated levels of Cathepsin B (CTSB) in conditioned medium derived from skeletal muscle cell cultures treated with AICAR. In cultured neural progenitor cells CTSB application enhanced expression of neurogenic markers. 

 

Analysis across species in mice, monkeys and humans showed that CTSB is upregulated in plasma with exercise. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function (Moon et al., 2016). Ongoing studies pertaining to the peripheral effects of exercise on brain function will also be discussed.