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Ageing causes prominent neurovascular dysfunction associated with loss of astrocytic contacts and gliosis
Author(s) -
Duncombe J.,
Lennen R. J.,
Jansen M. A.,
Marshall I.,
Wardlaw J. M.,
Horsburgh K.
Publication year - 2017
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12375
Subject(s) - neurovascular bundle , gliosis , microglia , pathology , medicine , neuroscience , biology , inflammation
Aims Normal neurovascular coupling, mediated by the fine interplay and communication of cells within the neurovascular unit, is critical for maintaining normal brain activity and cognitive function. This study investigated whether, with advancing age there is disruption of neurovascular coupling and specific cellular components of the neurovascular unit, and whether the effects of increasing amyloid (a key feature of Alzheimer's disease) would exacerbate these changes. Methods Wild‐type mice, in which amyloid deposition is absent, were compared to transgenic amyloid precursor protein ( APP ) littermates (TgSw DI ) which develop age‐dependent increases in amyloid. Baseline cerebral blood flow and responses to whisker stimulation were measured. Components of the neurovascular unit (astrocytes, end‐feet, pericytes, microglia) were measured by immunohistochemistry. Results Neurovascular coupling was progressively impaired with increasing age (starting at 12 months) but was not further altered in TgSw DI mice. Aged mice showed reduced vascular pericyte coverage relative to young but this was not related to neurovascular function. Aged mice displayed significant reductions in astrocytic end‐feet expression of aquaporin‐4 on blood vessels compared to young mice, and a prominent increase in microglial proliferation which correlated with neurovascular function. Conclusions Strategies aimed to restore the loss of astrocytic end feet contact and reduce gliosis may improve neurovascular coupling.