Creative Biolabs is dedicated to improving the understanding of the human central nervous system (CNS) disorders and developing effective and efficient therapeutic interventions. Especially, we offer rodent models of restless legs syndrome and offer contract efficacy studies in these models. With talented experts and scientists, we can help to select or customized the most appropriate models and assays as well as set up a detailed research plan based on the specific scientific needs.
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is a common and highly complex disorder with both sensory and motor symptoms. It is characterized by an intense urge to move the limbs, especially the legs. This urge has a circadian pattern, which is most pronounced in the evening or during the night and often relieved by walking. Nearly all RLS patients also suffer from the associated periodic limb movement of sleep (PLMS) and sleep disturbance. There may be several underlying pathophysiological pathways of RLS, among which 2 major impairments have been revealed. Firstly, abnormalities of the dopaminergic system have been observed by functional brain imaging and autopsy studies. Besides, the administration of dopaminergic agonists results in dramatic improvement of RLS symptoms while administration of dopaminergic antagonists worsens the symptoms, supporting the involvement of the dopaminergic system. Secondly, a major feature is the lack of iron in the substantia nigra of RLS patients. CNS iron dysregulation is strongly implicated by an inverse correlation between cerebrospinal fluid (CSF)/serum ferritin levels and RLS symptoms.
Fig.1 Proposed modulation of dopamine D1 receptors and D3 receptors in the spinal cord. (Trenkwalder et al. 2018)
Animal models can be used to evaluate various aspects of the etiology and manifestations in order to elucidate underlying disease mechanisms and their response to conventional and novel treatments. Based on the current theories of RLS pathogenesis, different rodent models have been developed and evaluated with regard to RLS.
Firstly, as the dopaminergic system is suggested to be implicated in the pathogenesis of RLS, models with dopamine-related deficits in brain function have been used, such as the neurotoxin 6-hydroxydopamine (6-OHDA) lesioned rat model. This model is found to partially mimic the clinical features of RLS. Secondly, due to the feature of iron deficiency in RLS patients, iron-deficient mice may provide a useful model for RLS. This can be induced by feeding mice with iron-deficient diets or by knocking out genes for iron regulation (e.g., D3 receptor knockout mice, Btbd9-deficient mice). Moreover, models of dopamine deficiency and iron deficiency can be combined to induce more severe RLS symptoms.
Creative Biolabs conducts contract studies in rodent RLS models and provides various outcome measures for evaluation of drug effect on RLS improvement. For instance, we can carry out locomotor activity measurements, iron level measurement in both serum and CNS, and neurological staining. In short, we offer assessments including but not limited to:
The neurological platform of Creative Biolabs provides an extensive range of rodent neurological disease models. If you are interested, click the following links for a more detailed description of each model:
Creative Biolabs fully understands what is needed, how far it is needed, and how to help design the studies to obtain rapid and clear answers to our clients. Our highly translatable disease models and key technologies will help progress your novel agents into the clinic. If you’re interested in our services, contact us to discuss your requirements.
Reference
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