Dados do Trabalho

Título

Possible neuroprotective mechanisms of exercise in improving sleep disorders caused by Restless Legs Syndrome in the iron-deficient rodent model

Introdução

Restless Legs Syndrome (RLS) is characterized by the need for movement, especially during rest and at night, which results in difficulty or inability to initiate and maintain sleep. The iron-deficient rodent model is a valuable model for understanding the changes and mechanisms of RLS, enabling the development of new therapies. Exercise is a strategy to improve symptoms, however it is little encouraged, and the mechanisms by which symptoms improve are poorly understood.

Objetivo

To investigate the effect of chronic aerobic exercise on the sleep pattern and architecture of animals, and to analyze the protein content of the dopamine receptor and transporter (D2R and DAT), adenosine receptors (A1R and A2R) and glutamate receptor (GLU1) in the striatum of the animal model of iron deficiency for RLS.

Métodos

Male Wistar rats were distributed into control group (CTRL) (standard diet), ID group (iron deficiency diet), CTRLEX (exercise) and IDEX (exercise) (n=6-7 per group). The exercise protocol was conducted in 5 sessions (1 hour each) per week, for 4 weeks. After 4 weeks of exercise, the animals’ sleep was evaluated for 24 hours, and striatum was collected for molecular analysis by Western Blot (WB). The results were analyzed using the linear mixed model, with post hoc Tukey (p<0.05).

Resultados

The ID group (group for RLS) demonstrated worsening in all sleep parameters expected for RLS (light cycle) in relation to the CTRL, with a reduction in total sleep time, sleep efficiency, and NREM sleep, and an increase in arousals, wakefulness and limb movements. The ID also showed an increase in the transition from wakefulness directly to REM sleep in relation to all groups (CTRL p=0.001; CTRLEX p=0.027; IDEX p=0.042), demonstrating a change in sleep architecture. The group that performed the exercise (IDEX) had improvements in all sleep parameters that were altered in the ID, with an increase in total sleep time (p<0.000), sleep efficiency (p<0.000), and NREM sleep (p=0.001), and a reduction in arousals (p=0.007), wakefulness (p<0.000) and limb movements (p<0.000). In addition, the exercise caused an increase in the DAT (p=0.001) and the A1R (p=0.001), which may represent changes responsible for the improvement in symptoms.

Conclusões

These results highlight the potential of exercise as a non-pharmacological treatment for sleep impairments caused by RLS and provide us with possible molecular pathways that act to improve sleep.
Acknowledgment: FAPESP (#2020/13074-6), Lilo Habersack Award 2021.

Palavras -chave

Sleep, Iron, Brain