Title : Impact of exercise intensity on cerebral BDNF levels: Role of FNDC5/Irisin
Abstract:
Physical exercise (EX) is an essential approach to improve physical and brain health. It is well known that positive effects of EX on brain involve the upregulation of cerebral BDNF (brain-derived neurotrophic factor), which promotes neuronal plasticity and cognitive functions. However, the underlying molecular mechanisms leading to an elevation of this neurotrophin remain not well known. One of these mechanisms is associated with myokine production induced by skeletal muscle contraction during EX. Recently, it has been reported that irisin, a peptide secreted into the blood and derived from the enzymatic cleavage of FNDC5 (Fibronectin type III domain-containing protein 5) was identified as a positive modulator of cerebral BDNF production. While the influence of EX intensity and modality on cerebral BDNF levels was characterized, the impact on muscular FNDC5/Irisin expression and circulating irisin level remains to be explored.
The experiments were conducted on adult male Wistar rats sedentary (SED, n= 6) or subjected to a horizontal treadmill exercise (EX, n= 18) protocol, 30 min/day for 7 consecutive days. The EX intensity was modulated by the speed of the treadmill set at 12 m/min for the EX12 (40% of maximal aerobic speed MAS), 14 m/min for the EX14 (50% of MAS), and 18m/min for the EX18 (70% of MAS) groups. Tissues were harvested 24 hours after the last EX session whereas blood was collected immediately. Expression of FNDC5/Irisin in oxidative muscle soleus (SOL) versus glycolytic muscle gastrocnemius (GAS) as well as hippocampal BDNF level were studied by both Western blotting and immunofluorescence methods. Serum irisin level was determined by the ELISA test.
Our data showed that 1) the increase in FNDC5/Irisin protein level was observed only in GAS and from a
corresponding threshold of 50% of MAS in EX compared to SED rats; 2) FNDC5/Irisin immunostaining was
localized only in fast-type fibers which are predominant in GAS 3) serum irisin level increased from EX at 50% of MAS and, 4) a positive correlation was obtained between serum irisin and hippocampal BDNF levels when SED and EX rats were studied simultaneously.
In conclusion, our study reveals that an intensity-dependent increase in hippocampal BDNF level is dependent on circulating irisin level and that the upregulation of FNDC5/Irisin expression is observed only in glycolytic muscle.
Audience Take Away
- The purpose of this study is to promote circulating irisin as a peripheral marker of cognitive abilities
- We believe that there will be a positive association between irisin blood levels and cognitive abilities in healthy subjects or patients with cognitive impairment. At the societal level, our findings will provide a strong case to promote brain health through physical exercise. At the scientific level, our results will allow to design exercise protocols able to improve cognition with a simple blood assay
