We describe age-related histological structure and molecular changes of the neurovascular unit (NVU) in the cerebral cortex of Tg2576 and age-matched wild-type (WT) mice. Major results can be summarized as follows: (i) β-amyloid (6E10)-immunoreactivity progressively increases in neurons and astrocytes of Tg2576 mice, reaching the highest concentration at 5 months and then decreasing as soon as extracellular plaque deposition begins; (ii) the synaptic puncta density of glutamatergic and GABAergic neurons in Tg2576 mice is unbalanced versus WT at all investigated ages, with a decrease in synaptophysin and VGLUT1; density of VGAT contacts is higher in 27-month-old Tg2576 versus WT mice; (iii) capillary density is higher in 5-month-old Tg2576 versus WT mice, then decreases to a lower density at 27 months, when the capillary-astrocyte interface is lower; and (iv) mRNA expression of genes involved in microvessel dynamics indicates age- and genotype-dependent changes in the expression levels of hypoxia-related genes, i.e. the highest level is in 5-month-old animals and there is impaired regulation in Tg2576. We conclude that at 5 months, when learning and memory impairment is already present in the absence of extracellular amyloid plaque deposition, Tg2576 mice display alterations in the structure and molecular regulation of the NVU.

Age-Related Changes of the Neurovascular Unit in the Cerebral Cortex of Alzheimer Disease Mouse Models: A Neuroanatomical and Molecular Study.

Giuliani A;Baldassarro VA;Lorenzini L;Sannia M;Calza L;Giardino L.
2019

Abstract

We describe age-related histological structure and molecular changes of the neurovascular unit (NVU) in the cerebral cortex of Tg2576 and age-matched wild-type (WT) mice. Major results can be summarized as follows: (i) β-amyloid (6E10)-immunoreactivity progressively increases in neurons and astrocytes of Tg2576 mice, reaching the highest concentration at 5 months and then decreasing as soon as extracellular plaque deposition begins; (ii) the synaptic puncta density of glutamatergic and GABAergic neurons in Tg2576 mice is unbalanced versus WT at all investigated ages, with a decrease in synaptophysin and VGLUT1; density of VGAT contacts is higher in 27-month-old Tg2576 versus WT mice; (iii) capillary density is higher in 5-month-old Tg2576 versus WT mice, then decreases to a lower density at 27 months, when the capillary-astrocyte interface is lower; and (iv) mRNA expression of genes involved in microvessel dynamics indicates age- and genotype-dependent changes in the expression levels of hypoxia-related genes, i.e. the highest level is in 5-month-old animals and there is impaired regulation in Tg2576. We conclude that at 5 months, when learning and memory impairment is already present in the absence of extracellular amyloid plaque deposition, Tg2576 mice display alterations in the structure and molecular regulation of the NVU.
Giuliani A, Sivilia S, Baldassarro VA, Gusciglio M, Lorenzini L, Sannia M, Calza L, Giardino L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/731206
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