BDNF trafficking and signaling impairment during early neurodegeneration is prevented by moderate physical activity

Abstract

Physical exercise can attenuate the effects of aging on the central nervous system by increasing the expression of neurotrophins such as brain-derived neurotrophic factor (BDNF), which promotes dendritic branching and enhances synaptic machinery, through interaction with its receptor TrkB. TrkB receptors are synthesized in the cell body and are transported to the axonal terminals and anchored to plasma membrane, through SLP1, CRMP2 and Rab27B, associated with KIF1B. Retrograde trafficking is made by EDH-4 together with dynactin and dynein molecular motors. In the present study it was found that early neurodegeneration is accompanied by decrease in BDNF signaling, in the absence of hyperphosphorylated tau aggregation, in hippocampus of 11 months old Lewis rats exposed to rotenone. It was also demonstrated that moderate physical activity (treadmill running, during 6 weeks, concomitant to rotenone exposure) prevents the impairment of BDNF system in aged rats, which may contribute to delay neurodegeneration. In conclusion, decrease in BDNF and TrkB vesicles occurs before large aggregate-like p-Tau are formed and physical activity applied during early neurodegeneration may be of relevance to prevent BDNF system decay.

Extracellular Vesicles: Delivery Vehicles of Myokines

“…Brain-derived neurotrophic factor has neurobiological and metabolic effects, regulating the survival (Hofer and Barde, 1988), growth (Kalcheim and Gendreau, 1988) and maintenance of neurons (Griesbeck et al, 1995). Its association with physical activity is already known (Almeida et al, 2016; Church et al, 2016); in fact, its expression not only increases after exercise (Park and Kwak, 2017) but also depends on the intensity of exercise (Jeon and Ha, 2017). Previous studies demonstrated that its mRNA and protein expression levels increase in human skeletal muscle after exercise without any release into the circulation (Matthews et al, 2009).…”

Moderate Exercise Combined with Enriched Environment Enhances Learning and Memory through BDNF/TrkB Signaling Pathway in Rats

“…On the other hand, whereas regular physical activity benefits learning and memory over the whole life course, the benefits are dependent on aspects of physical exercise plans such as speed, time or slope [16][17][18]. For instance, moderate treadmill exercise was shown to positively modulate the concentrations of BDNF and its TrkB receptor in experimental animals [19,20]. Therefore, the different exercise intensities have different effects on learning and memory as well as BDNF/TrkB signaling activities.…”

Exposure to RF-EMF Alters Postsynaptic Structure and Hinders Neurite Outgrowth in Developing Hippocampal Neurons of Early Postnatal Mice

“…Reduced BDNF expression in hippocampal neurons causes a decrease in neurite outgrowth [ 51 ]. MAP2 is a neuron-specific cytoskeletal protein that stabilizes microtubules and is involved in establishing dendritic arborization during development.…”