title: Early selective vulnerability of synapses and synaptic mitochondria in the hippocampal CA1 region of the Tg2576 mouse model of Alzheimer's disease.
abstract: Increasing experimental evidence indicates that synaptic alterations play a key role in cognitive decline in Alzheimer's disease (AD). Functional and structural synaptic changes progressively take place, beginning in the early phase of AD, mainly triggered by intracellular accumulation of soluble amyloid-β (Aβ) oligomers. These peptides also accumulate within mitochondria, heavily affecting their function and morphology, particularly in synaptic compartments. To better understand the role of mitochondrial impairment in synaptic alterations during the early stages of AD, a morphological investigation was performed by means of electron microscopy in the hippocampus of 3 month-old Tg2576 and transgene-negative littermate mice. In the stratum moleculare of CA1 pyramidal cells (SMCA1) of transgenic animals compared to controls, we found significantly larger and less numerous synapses, with a significantly reduced fraction of the perforated subtype, as well as significantly smaller and more numerous mitochondria. In contrast, no differences between the two groups of mice were found in the inner molecular layer of the dentate gyrus. The reduction of synaptic contacts in SMCA1 indicates a precocious vulnerability of this region, and the synaptic enlargement may reflect a compensating process aimed at maintaining the overall contact density. Accordingly, mitochondrial modifications may represent a plastic reactive phenomenon aimed at sustaining the increased energy needs for synaptic remodeling, since mitochondrial morphology was perfectly preserved and smaller mitochondria are metabolically more efficient. Thus, morphological changes occurring at synaptic level in SMCA1 of 3 month-old Tg2576 mice might reflect a precocious vulnerability associated with a residual plastic reactivity which may slow down functional alterations.
authors: Neurobiology of Aging Centre, INRCA, Ancona, Italy Cellular Bioenergetics Laboratory, INRCA, Ancona, Italy. m.balietti@inrca.it
authors: Marta
authors: M
authors: Balietti
authors: Belinda
authors: B
authors: Giorgetti
authors: Tiziana
authors: T
authors: Casoli
authors: Moreno
authors: M
authors: Solazzi
authors: Francesco
authors: F
authors: Tamagnini
authors: Costanza
authors: C
authors: Burattini
authors: Giorgio
authors: G
authors: Aicardi
authors: Patrizia
authors: P
authors: Fattoretti
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D053764:Presenilin-1 / Q000235:genetics; D013569:Synapses / Q000473:pathology* / Q000648:ultrastructure*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1