Problem
Down syndrome (DS) is a developmental disability that is strongly associated with atypical tongue movement and positioning. This is implicated in difficulties of speech, eating, drinking, swallowing, and breathing that can occur in children with DS. These difficulties can be very complex and challenging to treat.
Solution
A solution to this problem uses mouse models of DS to establish experimental frameworks clarifying how the tongue changes during early childhood in typical development, and how these changes are impacted by DS. This will lay the foundation for using animal models for pre-clinical research to develop or refine therapeutics to ameliorate challenges of tongue movement for people with DS.
Figure 1. Excerpt from a tissue section demonstrating the arrangement of major muscles of the intrinsic tongue. Blue staining indicates Myosin Heavy Chain isoform 2B, and red staining indicates Myosin Heavy Chain isoform 2A.
The tongue is unlike any other muscle in the human body. The tongue is comprised of several different muscles that interdigitate. The intrinsic tongue refers to the part of the interdigitating tongue muscles that are located in the oral cavity. These muscles include the superior longitudinal muscle, the inferior longitudinal muscle, the transverse muscle, and the verticalis muscle (Figure 1). In addition to contributing to tongue movement and tongue shape changes, these muscles may also have unique biological properties in their anterior, middle, and posterior regions. Because of the anatomical complexity of how fibers from these muscles interdigitate and change across anatomical regions, the intrinsic tongue has historically been regarded as a technically difficult structure to study, and disorders of tongue function remain challenging to manage and treat.
Intrinsic tongue muscles change rapidly during postnatal maturation. The current dataset was generated to study early postnatal changes in intrinsic tongue muscles in the Ts65Dn mouse model of DS and controls at three different young ages. Each age represents a distinct maturational stage in which the tongue functions required for eating and drinking are developmentally unique. These ages coincide with the oral motor developmental stages of 1) nursing, 2) weaning to solid food, and 3) mature eating and drinking behavior (Figure 2). This high-resolution dataset of intact intrinsic tongue muscle tissue sections is the most anatomically comprehensive study of tongue muscle biology in DS to date. Sections from the three young ages are from male and female Ts65Dn mice and euploid sibling controls.
Figure 2. Representative tissue sections demonstrate myofiber characteristics associated with maturational age and anatomical region. Anterior expression of MyHC 2b initiates at weaning, and extends to posterior regions with maturation. Figure excerpt from: Glass et al, 2024. Front. Neurol., 10 December 2024. Sec. Pediatric Neurology. Volume 15 – 2024. https://doi.org/10.3389/fneur.2024.1461682
Impact
The addition of a comprehensive anatomical dataset of high-resolution intrinsic tongue images from a mouse model of DS is a step toward including more members of the rapidly growing DS research community in the work of the Stimulating Peripheral Activity to Relieve Conditions (SPARC) portal. This may contribute to efforts to improve understanding of how nerves and tongue muscles interact, thereby accelerating development or refinement of the use of therapeutic devices that modulate electrical activity in nerves to improve tongue function. The hypoglossal nerve directs movement of the tongue muscles, and hypoglossal nerve stimulation is emerging as a promising clinical treatment avenue for sleep apnea in children with DS.
