Region-specific changes in the microanatomy of single dendritic spines over time might account for selective memory alterations in ageing hAPPsweTg2576 mice, a mouse model for Alzheimer disease.
Tg2576 mice over-expressing human mutant APP (hAPPswe) show progressive impairments in hippocampal plasticity and episodic memory while fronto-striatal plasticity and procedural memory remain intact. Here we examine the status of synaptic connectivity in the hippocampus and the dorsolateral striatum (DLS) of 3- and 15-month-old Tg2576 and wild-type mice through the analysis of single dendritic spines microanatomy. We found that, in each region, all mice showed a global reduction in the size of spines as a function of age. Ageing mutants, however, exhibited smaller spines with shorter necks on CA1 pyramidal neurons but larger spines with longer necks on DLS spiny neurons compared to their age-matched wild-type controls. Our findings indicate that hippocampal and DLS dendritic spines in hAPPswe mutants undergo a different pattern of morphological changes over time and point to minor alterations in the microanatomy of DLS spines as a compensatory mechanism maintaining procedural abilities in the ageing mutants.
CNR Institute for Neuroscience, S. Lucia Foundation, Via del Fosso di Fiorano 64/65, 00143 Rome, Italy. s.middei@hsantalucia.it
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Middei
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Restivo
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Caprioli
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Aceti
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Ammassari-Teule
D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology; D004252:DNA Mutational Analysis; D049229:Dendritic Spines / Q000648:ultrastructure*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009415:Nerve Net / Q000473:pathology; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000473:pathology
D016564:Amyloid beta-Protein Precursor