BDNF-TrkB signaling inhibits microglial activation: countering effect of aging and exercise

Abstract

Aging inflammation and reduced brain-derived neurotrophic factor (BDNF) are associated with dopaminergic neuron loss in the substantia nigra However the causal relationships are unclear We found age-related dopaminergic neuron loss lower in mice with inhibited microglial activation BDNF and BDNF-receptor TrkB levels were positively correlated with the number of dopaminergic neurons and negatively with the degree of microglial activation Lipopolysaccharide-induced microglial activation was attenuated by BDNF while BDNF-induced antimicroglial activation was inhibited by shTrkB treatment In mice forced to exercise which upregulates BDNF and TrkB age-related microglial activation and dopaminergic neuron loss were inhibited Microglial activation was higher and exercise-induced protection lower in mice treated with shTrkB In conclusion our findings suggest a three-way reciprocal regulation among dopaminergic neurons BDNF and microglia Aging disrupts the balances among them and favors microglial activation BDNF-TrkB signaling was upregulated and age-related microglial activation and dopaminergic neuron death were inhibited in mice forced to undergo long-term exercise

Date of Award	2016 Jun 20
Original language	English
Supervisor	Yu-Min Kuo (Supervisor)