Effect of the Myokine Irisin on Circadian Rhythm of Voluntary Locomotor Activity in Rats

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The endogenous circadian oscillator located in the suprachiasmatic nucleus of mammals, generates its own rhythm, the period of which usually does not correspond exactly to the 24h-duration of the day, and therefore needs to be synchronised with the geophysical daily rhythm of the surrounding word. Within one of the most important non-photic mechanisms of synchronisation of the circadian clock, their entrainment is based on information about the schedule and intensity of physical activity. The role of the key molecular synchronising factor in this mechanism is attributed to the myokine irisin however, the effects of irisin on the behavioural circadian rhythms remain unexplored. In the present work, the effect of three-time intranasal administration of 0.5 μg irisin under constant darkness at different projected moments of three consecutive daily cycles (ZT 2, ZT 6, ZT 10, ZT 14, ZT 18 and ZT 22) on the circadian rhythm of voluntary locomotor activity in a running wheel was studied for the first time in experiments on male Wistar rats. The administration of irisin at ZT 6 induced a statistically significant advanced phase shift of the rhythm acrophase median of 0.60 hours (p < 0.05), accompanied by a decrease in gross locomotor activity by 1666-wheel revolutions per day (p < 0.05). Intranasal administration of irisin at any other moment of the projected daily cycle did not lead to statistically significant phase shift in circadian rhythm or change in total locomotor activity. Irisin did not induce changes in the circadian rhythm period regardless of the time of administration. The obtained results are an experimental confirmation of the role of endogenous irisin as a factor of non-photic synchronization of circadian clock of the suprachiasmatic nucleus, manifested itself in the absence of the main physiological timekeeper – cyclic afferentation from the retinal photoreceptors, in accordance with the daily schedule and intensity of muscle activity within the functional axis “muscles-brain”.

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A. Inyushkin

Samara National Research University

编辑信件的主要联系方式.
Email: ainyushkin@mail.ru
俄罗斯联邦, Samara

T. Isakova

Samara National Research University

Email: ainyushkin@mail.ru
俄罗斯联邦, Samara

A. Konashenkova

Samara National Research University

Email: ainyushkin@mail.ru
俄罗斯联邦, Samara

E. Inyushkina

Samara National Research University

Email: ainyushkin@mail.ru
俄罗斯联邦, Samara

A. Inyushkin

Samara National Research University

Email: ainyushkin@mail.ru
俄罗斯联邦, Samara

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2. Fig. 1. An example of the response of the circadian rhythm of voluntary locomotor activity to a triple intranasal administration of 0.5 μg irisin at ZT 6. The actigram is presented as a daily (24-hour) raster, so that each row contains data for each consecutive day of the experiment with a total duration of 31 days. The vertical lines correspond to the number of revolutions of the running wheel in consecutive 5-second time intervals. The periods of light on are shown with a light background, the periods of darkness with a dark background. The moments of irisin administration are marked with asterisks and correspond to ZT 6. After the triple administration of irisin, a shift in the rhythm of locomotor activity occurred towards an advance, which in total amounted to 3.19 h in this experiment.

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3. Fig. 2. Statistical data on the effect of triple intranasal administration of 0.5 μg irisin at ZT 6 on the parameters of the circadian rhythm of voluntary locomotor activity. The abscissa axis shows data for 7 days preceding the administration of irisin (Before) and 7 days after administration (Irisin), the ordinate axis shows the period, h (a), acrophase, h (b), and the total activity of treadmill revolutions for 7 days (c).

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4. Fig. 3. An example of an actigram of the circadian rhythm of voluntary locomotor activity under conditions of triple intranasal administration of 0.5 μg irisin in ZT 14. All designations are as in Fig. 1.

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5. Fig. 4. An example of an actigram of the circadian rhythm of voluntary locomotor activity under conditions of three-fold intranasal administration of 2 × 10 μl of water for injection in ZT 6 (control). All designations are as in Fig. 1.

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6. Fig. 5. Phase shifts of the circadian rhythm of voluntary locomotor activity caused by triple intranasal administration of irisin (a) and water for injection (b, control) at different moments of the projected daily cycle. The abscissa axis shows the moment of administration (ZT), the ordinate axis shows the severity of the phase shift, h (positive values – leading shift, negative values – lagging shift). * p < 0.05 (Mann–Whitney rank test).

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