Changes in motor behavior during pregnancy in rats: the basis for a possible animal model of restless legs syndrome

Abstract

PURPOSE: Pregnant women have a 2-3 fold higher probability of developing restless legs syndrome (RLS -sleep-related movement disorders) than general population. This study aims to evaluate the behavior and locomotion of rats during pregnancy in order to verify if part of these animals exhibit some RLS-like features. METHODS: We used 14 female 80-day-old Wistar rats that weighed between 200 and 250 g. The rats were distributed into control (CTRL) and pregnant (PN) groups. After a baseline evaluation of their behavior and locomotor activity in an open-field environment, the PN group was inducted into pregnancy, and their behavior and locomotor activity were evaluated on days 3, 10 and 19 of pregnancy and in the post-lactation period in parallel with the CTRL group. The serum iron and transferrin levels in the CTRL and PN groups were analyzed in blood collected after euthanasia by decapitation. RESULTS: There were no significant differences in the total ambulation, grooming events, fecal boli or urine pools between the CTRL and PN groups. However, the PN group exhibited fewer rearing events, increased grooming time and reduced immobilization time than the CTRL group (ANOVA, p<0.05). CONCLUSION: These results suggest that pregnant rats show behavioral and locomotor alterations similar to those observed in animal models of RLS, demonstrating to be a possible animal model of this sleep disorder. ResumoOBJETIVO: Mulheres grávidas apresentam de duas a trêz vezes maior probabilidade de desenvolver a Síndrome das Pernas Inquietas (SPI -distúrbio do movimento relacionado ao sono) do que a população geral. O objetivo do estudo foi avaliar o comportamento e a locomoção de ratas durante a gravidez, a fim de verificar se esses animais apresentam algumas características SPI-like. MÉTODOS: Foram utilizadas 14 fêmeas Wistar de 80 dias de idade, pesando entre 200 e 250 g. Os ratos foram distribuídos em grupos controle (CTRL) e prenhes (PN). Após uma avaliação inicial do comportamento e da atividade locomotora em um ambiente de campo aberto, o grupo PN foi introduzido a prenhez, e sua atividade e comportamento locomotor foram avaliados nos dias 3, 10 e 19 de prenhez e no período pós-lactação em paralelo ao grupo CTRL. Os níveis de ferro e transferrina séricos nos grupos CTRL e PN foram analisados em sangue coletado após eutanásia por decapitação. RESULTADOS: Não houve diferenças significativas na deambulação total, nos eventos de grooming, bolos fecais e urina entre os grupos CTRL e PN. No entanto, o grupo PN apresentou menos eventos de rearing, aumento no tempo de duração de grooming e redução no tempo de imobilização em relação ao grupo CTRL (ANOVA, p<0,05). CONCLUSÃO: Esses resultados sugerem que ratas prenhes apresentam alterações comportamentais e locomotoras semelhantes às observadas em modelos animais de SPI, demonstrando ser um possível modelo animal desse distúrbio do sono.

Consensus guidelines on the construct validity of rodent models of restless legs syndrome

“…Genetically modified rodents have already been studied individually for their ability to recapitulate several RLS pathogenetic mechanisms and RLS-like behavioral phenotypes ( DeAndrade et al, 2012 ; Drgonova et al, 2015 ; Salminen et al, 2017 , 2019 ; Lyu et al, 2019a , 2020a ). In addition, PID during the post-weaning period – either alone or in combination with hypoxia or pregnancy – has been used to reproduce the RLS-like behavioral phenotype in rodents ( Mariano et al, 2014 ; Lo Martire et al, 2018 ; Lai et al, 2017 ). Other potential methods, such as renal failure and CNS-active medications, remain to be studied in the context of RLS.…”

“…However, this may not correspond biologically to the third trimester of human pregnancy and, therefore, the interpretation of such results is challenging. One study has investigated the motor behavior of pregnant rats as a potential model for RLS ( Mariano et al, 2014 ).…”

Iron deficiency in pregnancy: Influence on sleep, behavior, and molecular markers of adult male offspring

“…Studies with other animal models of RLS showed changes in the sleep pattern, also related to RLS symptoms in humans, such as increased wakefulness (DeAndrade et al, 2012) and leg movements at the end of the dark period (Lopes et al, 2012). Mariano et al (2014) showed RLS-related behavioral changes in pregnant rats, and so far, it is the only study that used pregnant rats as a possible animal model for RLS, since pregnancy is one of the critical periods for the onset of this disorder and generates iron deficiency (Manconi et al, 2004;Picchietti et al, 2015).…”