High Intensity Acute Aerobic Exercise Elicits Alterations in Circulating and Skeletal Muscle Tissue Expression of Neuroprotective Exerkines.

Background: Cathepsin B (CTSB) and brain derived neurotrophic factor (BDNF) are increased with aerobic exercise (AE) and skeletal muscle has been identified as a potential source of secretion. However, the intensity of AE and the potential for skeletal muscle contributions to circulating CTSB and BDNF have not been fully studied in humans.

Objective: Determine the effects of AE intensity on circulating and skeletal muscle CTSB and BDNF expression profiles.

Methods: Young healthy subjects (n = 16) completed treadmill-based AE consisting of VO₂max and calorie-matched acute AE sessions at 40%, 65% and 80% VO₂max. Fasting serum was obtained before and 30-minutes after each bout of exercise. Skeletal muscle biopsies (vastus lateralis) were taken before, 30-minutes and 3-hours after the 80% bout. Circulating CTSB and BDNF were assayed in serum. CTSB protein, BDNF protein and mRNA expression were measured in skeletal muscle tissue.

Results: Serum CTSB increased by 20±7% (p = 0.02) and 30±18% (p = 0.04) after 80% and VO₂max AE bouts, respectively. Serum BDNF showed a small non-significant increase (6±3%; p = 0.09) after VO₂max. In skeletal muscle tissue, proCTSB increased 3 h-post AE (87±26%; p < 0.01) with no change in CTSB gene expression. Mature BDNF protein decreased (31±35%; p = 0.03) while mRNA expression increased (131±41%; p < 0.01) 3 h-post AE. Skeletal muscle fiber typing revealed that type IIa and IIx fibers display greater BDNF expression compared to type I (p = 0.02 and p < 0.01, respectively).

Conclusions: High intensity AE elicits greater increases in circulating CTSB compared with lower intensities. Skeletal muscle protein and gene expression corroborate the potential role of skeletal muscle in generating and releasing neuroprotective exerkines into the circulation.NEW AND NOTEWORTHY: 1) CTSB is enriched in the circulation in an aerobic exercise intensity dependent manner. 2) Skeletal muscle tissue expresses both message and protein of CTSB and BDNF. 3) BDNF is highly expressed in glycolytic skeletal muscle fibers.