Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

By R. Bell, E. Winkler, A. Sagare, Itender Singh, Barbra LaRue, R. Deane, Berislav Zlokovic. Neuron, 2010

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SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration.

Subfields: Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/46b504a7d777b5d8df525903eabfb26ea263b32c

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Citations in the corpus

The blood-brain barrier: an engineering perspective (2013, background): “…cells binds with the corresponding Frontiers in Neuroengineering www.frontiersin.org August 2013 | Volume 6 | Article 7 | 5 receptor (PDGFR-B) on pericytes, regulating recruitment of pericytes as well as their proliferation (Bell et al., 2010; Dalkara et al., 2011; Winkler et al., 2011).”
Role of neuroinflammation in neurodegeneration development (2023, background): “In addition, deficient PDGFRβ signaling in AD also can lead to pericyte loss causing BBB disruption independently of Aβ.(505) In vitro cultured pericytes were suggested to rapidly clear extracellular Aβ40 via LRP1, while excessive accumulation of Aβ in pericytes over longer periods of time resulted ”
The pathobiology of vascular dementia (2013, positive): “In capillaries, smooth muscle cells are replaced by pericytes, contractile cells that are particularly abundant in brain vessels and are involved in the development and maintenance of the BBB (Armulik et al., 2010; Bell et al., 2010; Quaegebeur et al., 2011).”
Current Strategies for Brain Drug Delivery (2018, background): “In addition to astrocytes, studies have also shown that pericytes decrease with age, accompanying the increase in BBB permeability [101].”
The blood-brain barrier in Alzheimer's disease (2017, neutral): “Pericyte dysfunction is associated with AD neuropathology (Bell et al., 2010; Zlokovic, 2011; Bell et al., 2012; Sagare et al., 2013; Sengillo etal.,2013;Winkleretal.,2014;Montagneetal.,2015).”