HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Morphological alterations in the hippocampus of the Ts65Dn mouse model for Down syndrome correlate with structural plasticity markers

Olga Villarroya1, Raúl Ballestín1, Rosa López-Hidalgo1, Maria Mulet1, José Miguel Blasco-Ibáñez1, Carlos Crespo1, Juan Nacher1,2,3, Javier Gilabert-Juan1,4 and Emilio Varea1

1Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de València, 2Fundación Investigación Hospital Clínico de Valencia, INCLIVA, 3CIBERSAM: Spanish National Network for Research in Mental Health and 4Genetics Department, Universitat de València, CIBERSAM, Valencia, Spain


Offprint requests to: Emilio Varea, Neurobiology Unit, Cell Biology Department, Universitat de València, Dr. Moliner, 50, Burjassot 46100, Spain. e-mail: emilio.varea@uv.es


Summary. Down syndrome (DS) is the most common chromosomal aneuploidy. Although trisomy on chromosome 21 can display variable phenotypes, there is a common feature among all DS individuals: the presence of intellectual disability. This condition is partially attributed to abnormalities found in the hippocampus of individuals with DS and in the murine model for DS, Ts65Dn. To check if all hippocampal areas were equally affected in 4-5 month adult Ts65Dn mice, we analysed the morphology of dentate gyrus granule cells and cornu ammonis pyramidal neurons using Sholl method on Golgi-Cox impregnated neurons. Structural plasticity has been analysed using immunohistochemistry for plasticity molecules followed by densitometric analysis (Brain Derived Neurotrophic Factor (BDNF), Polysialylated form of the Neural Cell Adhesion Molecule (PSA-NCAM) and the Growth Associated Protein 43 (GAP43)). We observed an impairment in the dendritic arborisation of granule cells, but not in the pyramidal neurons in the Ts65Dn mice. When we analysed the expression of molecules related to structural plasticity in trisomic mouse hippocampus, we observed a reduction in the expression of BDNF and PSA-NCAM, and an increment in the expression of GAP43. These alterations were restricted to the regions related to dentate granule cells suggesting an interrelation. Therefore the impairment in dendritic arborisation and molecular plasticity is not a general feature of all Down Syndrome principal neurons. Pharmacological manipulations of the levels of plasticity molecules could provide a way to restore granule cell morphology and function. Histol Histopathol 33, 101-115 (2018)

Key words: PSA-NCAM, BDNF, GAP43, Granule cells, CA1 pyramidal neurons

DOI: 10.14670/HH-11-894