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RESEARCH PRODUCT

Alterations in reelin and reelin receptors in Down syndrome.

Josep CarbonellCarlos CrespoMiguel BellésJosé Miguel Blasco-ibáñezJuan NacherEmilo Varea

subject

0301 basic medicineNervous systemAdultMaleReceptor expressionCell Adhesion Molecules NeuronalNerve Tissue ProteinsReceptors Cell SurfaceTissue BanksInhibitory postsynaptic potential03 medical and health sciencesMice0302 clinical medicinemedicineAnimalsHumansReelinReceptorLDL-Receptor Related ProteinsAgedTemporal cortexNeuronsExtracellular Matrix ProteinsbiologyCell adhesion moleculeGeneral NeuroscienceSerine EndopeptidasesMiddle AgedTemporal LobeCell biologyDisease Models AnimalReelin Protein030104 developmental biologymedicine.anatomical_structurenervous systemReceptors LDLbiology.proteinDown Syndrome030217 neurology & neurosurgeryLipoprotein

description

Reelin is an extracellular matrix glycoprotein that modulates synaptic function and plasticity, with a crucial role in neuronal migration. Changes in the expression of this protein have been reported in neurodegenerative diseases, such as Alzheimer's disease (AD). This molecule is produced by Cajal-Retzius neurons during development and by inhibitory neurons in the adult nervous system. Individuals with Down syndrome (DS) present an early development of AD; therefore, we analyzed the alterations in this molecule and its receptors in the murine model for DS Ts65Dn as well as in human with DS. We performed immunofluorescence analysis for reelin and its receptors very-low-density lipoprotein receptor and apolipoprotein R receptor 2 in the temporal cortex of mice and humans and have quantified the density of reelin-expressing neurons and the intensity of expression of both receptors. We have observed an increment in the density of reelin immunoreactive neurons in both the temporal cortex of adult Ts65Dn mice and humans with DS. Moreover, these reelin immunoreactive neurons displayed a disorganized distribution when compared with wild-type mice. Regarding reelin receptors, very-low-density lipoprotein receptor expression remained unaltered in both Ts65Dn and humans with DS, whereas apolipoprotein R receptor 2 decreased in both individuals with DS and Ts65Dn mice. These alterations are similar to those observed in individuals with AD.

10.1097/wnr.0000000000001153https://pubmed.ncbi.nlm.nih.gov/30395007