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.2022 Oct 21;8(1):5-18.
doi: 10.3233/BPL-220137. eCollection 2022.

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

Affiliations

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

Corey E Mazo et al. Brain Plast..

Abstract

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 andp < 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.

Keywords: Human; brain derived neurotrophic factor; cathepsin B.

© 2022 – The authors. Published by IOS Press.

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Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Effects of Acute Aerobic Exercise Intensity on Circulating CTSB. Circulating CTSB before and 30-minutes post AE A) 40% of VO2max, B) 65% of VO2max, C) 80% of VO2max and D) at VO2max.n = 15 (9M/6F) 80% VO2max,n = 16 (10M/6F) all other timepoints. All data are represented as mean±SEM.*p < 0.05 vs PRE.
Fig. 2
Fig. 2
Effects of Acute Aerobic Exercise Intensity on Circulating BDNF. Circulating BDNF before and 30-minutes post AE A) 40% of VO2max, B) 65% of VO2max, C) 80% of VO2max and D) at VO2max.n = 15 (9M/6F) 80% VO2max,n = 16 (10M/6F) all other timepoints. All data are represented as mean±SEM.
Fig. 3
Fig. 3
CTSB Skeletal Muscle Protein and Transcript Response to 80% Acute Aerobic Exercise. A) Representative western blot probing for CTSB before, 30-minutes post and 3-hours post 80% acute AE. All samples were normalized to total protein stain. Protein and transcript content of B) Mature CTSB protein, C) ProCTSB protein, D) Total CTSB protein and E) Pro:Mature CTSB protein ratio and F) CTSB transcriptn = 15 (8M/7F). Mature CTSB is expected at 30 kD, ProCTSB is expected at 41 KD. All data are represented as mean±SEM.n = 13 PRE (7M/6F),n = 6 POST (5M/1F), andn = 6 3 h (4M/2F).*p < 0.05 vs PRE,**p < 0.01 vs PRE,#p < 0.05 main effect of time.
Fig. 4
Fig. 4
BDNF Skeletal Muscle Protein and Transcript Response to 80% Acute Aerobic Exercise. A) Representative western blot probing for BDNF before, 30-minutes post and 3-hours post 80% acute AE. All samples were normalized to total protein stain. Protein and transcript content of B) Mature BDNF protein, C) ProBDNF protein, D) Total BDNF protein and E) Pro:Mature BDNF protein ratio and F) BDNF transcriptn = 15 (8M/7F). Mature BDNF is expected at 15 kD, Pro BDNF is expected at 30 kD. All data are represented as mean±SEM.n = 13 PRE (7M/6F),n = 8 POST (5M/3F), andn = 8 3 h (4M/4F).*p < 0.05 vs PRE,**p < 0.01 vs PRE,#p < 0.05 main effect of time.
Fig. 5
Fig. 5
Skeletal Muscle Fiber Type Analysis of BDNF. A) Representative image of skeletal muscle fiber type and B) BDNF. C) BDNF relative intensity per fiber type. Red fibers = MHC I, white fibers = MHC IIa and black fibers = MHC IIx All data are represented as mean±SEM.n = 11 (7M/4F) for MHC I and IIa,n = 10 (6M/4F) for MHC IIx.*p < 0.05,**p < 0.01.
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