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ASSOCIATIONS BETWEEN DOPAMINE TRANSPORTER AND LIMB MOVEMENT IN AN IRON DEFICIENCY ANIMAL MODEL OF RESTLESS LEGS SYNDROME
Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by discomfort in the legs at night. Among the main causes of RLS is the alteration in brain iron homeostasis, causing dopaminergic dysfunction, with alterations in the dopamine transporter (DAT), in the receptor (D2), and in the tyrosine hydroxylase (TH). Symptoms of akathisia and leg movements during sleep are elements of response to changes in the dopamine system. However, the role of DAT in the pathophysiology of RLS is still uncertain. The iron-deficient rodent model provides us with a valuable model to understand the neurochemical changes and mechanisms of RLS, enabling the development of new therapies.
Thus, the aim of the present study was to analyze DAT, D2, TH, and sleep architecture of the iron-deficient RLS rodent model.
Wistar rats were used and distributed into control (CTRL) and iron deficient (DFe) groups. The diet used was AIN93M, with manipulation in the mineral mix for the DFe group (<3mg/kg of iron). After 10 weeks of diet, stereotaxic surgery was performed to analyze the sleep record (9 am-12 am). The striatum of the animals was collected for molecular analysis by real-time Polymerase Chain Reaction (PCR) and Western Blot (WB) of the dopaminergic system.
The results showed that DFe rats have low serum iron determinations and high transferrin values compared to the control group. Animals that received an iron-deficient diet showed increased limb movements during sleep, reduced DAT gene expression, and increased DAT protein content. Serum iron and ferritin concentrations were negatively correlated with animal limb movements and DAT gene expression showed a positive correlation for total sleep time, sleep efficiency, and slow wave sleep time.
In conclusion, the results suggest that DFe rats showed signs of RLS, demonstrated by alterations in sleep architecture, such as increased limb movements, and by molecular alterations, with a reduction in the DAT associated with alterations in the animals' sleep architecture.
Restless legs syndrome, iron-deficient, sleep
Beatriz Franco, Alessandro Spencer de Souza Holanda, Giovanna Antonella Martineli Rodrigues, Milca Abda de Morais, Alana Carolina Costa Veras, Marcio Alberto Torsoni, Letícia Martins Ignácio-Souza, Adriana Souza Torsoni, Andrea Maculano Esteves