Synaptic deficit in the temporal cortex of partial trisomy 16 (Ts65Dn) mice.
Down syndrome results from triplication of human chromosome 21. The distal end of mouse chromosome 16 shares a large region of genetic homology with the Down syndrome 'critical region' of human chromosome 21. Therefore, a partially trisomic mouse (Ts65Dn) that possesses a triplication of the distal region of chromosome 16 has been developed as a putative model for Down syndrome. Ts65Dn mice display learning and memory deficits. However, despite the importance of preserved synaptic integrity for learning and memory, the ultrastructure of neural connectivity has not yet been studied in Ts65Dn mice. Therefore, the density and apposition zone length of synapses in the temporal cortex of aged Ts65Dn mice (n=4) were compared with those in diploid controls (n=4), using quantitative electron microscopy. There were significantly less (30%) asymmetric synapses in the temporal cortex of Ts65Dn mice than in controls (t=-5.067; p=0.023). However, there was no significant difference between the mean density of symmetric synapses in Ts65Dn mice and control mice. In addition, the mean synaptic apposition lengths of both asymmetric (15%; t=9.812, p<0.0001) and symmetric (11%; t=5. 582; p<0.0001) synapses were significantly larger in Ts65Dn mice than in controls. These results suggest that excitatory synapses are preferentially affected in Ts65Dn mice and that there is an attempt to compensate for the deficit of asymmetric synapses by increasing the contact zone area of existing synapses. The results may also reveal the morphological basis for the learning and memory deficits observed in Ts65Dn mice and have a bearing on the cognitive deficits in Down syndrome in old age.
Kurt
M A
MA
Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, Cranmer Terrace, Tooting, London, UK.
Davies
D C
DC
Kidd
M
M
Dierssen
M
M
Flórez
J
J
D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D013569:Synapses / Q000648:ultrastructure*; D013702:Temporal Lobe / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure*; D014314:Trisomy / Q000235:genetics / Q000473:pathology*