PMID- 31333445
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 11
DP  - 2019
TI  - 3D Reconstruction of the Neurovascular Unit Reveals Differential Loss of 
      Cholinergic Innervation in the Cortex and Hippocampus of the Adult Mouse Brain.
PG  - 172
LID - 10.3389/fnagi.2019.00172 [doi]
LID - 172
AB  - Increasing evidence supports a role for cerebrovasculature dysfunction in the 
      etiology of Alzheimer's disease (AD). Blood vessels in the brain are composed of 
      a collection of cells and acellular material that comprise the neurovascular unit 
      (NVU). The NVU in the hippocampus and cortex receives innervation from 
      cholinergic neurons that originate in the basal forebrain. Death of these neurons 
      and their nerve fibers is an early feature of AD. However, the effect of the loss 
      of cholinergic innervation on the NVU is not well characterized. The purpose of 
      this study was to evaluate the effect of the loss of cholinergic innervation of 
      components of the NVU at capillaries, arteries and veins in the hippocampus and 
      cortex. Adult male C57BL/6 mice received an intracerebroventricular injection of 
      the immunotoxin p75NTR mu-saporin to induce the loss of cholinergic neurons. 
      Quadruple labeling immunohistochemistry and 3D reconstruction were carried out to 
      characterize specific points of contact between cholinergic fibers and collagen 
      IV, smooth muscle cells and astrocyte endfeet. Innate differences were observed 
      between vessels of the hippocampus and cortex of control mice, including a 
      greater amount of cholinergic contact with perivascular astrocytes in hippocampal 
      capillaries and a thicker basement membrane in hippocampal veins. Saporin 
      treatment induced a loss of cholinergic innervation at the arterial basement 
      membrane and smooth muscle cells of both the hippocampus and the cortex. In the 
      cortex, there was an additional loss of innervation at the astrocytic endfeet. 
      The current results suggest that cortical arteries are more strongly affected by 
      cholinergic denervation than arteries in the hippocampus. This regional variation 
      may have implications for the etiology of the vascular pathology that develops in 
      AD.
FAU - Nizari, Shereen
AU  - Nizari S
AD  - School of Life, Health and Chemical Science, Faculty of Science, Technology, 
      Engineering and Mathematics, The Open University, Milton Keynes, United Kingdom.
FAU - Carare, Roxana O
AU  - Carare RO
AD  - Clinical and Experimental Sciences, Faculty of Medicine, University of 
      Southampton, Southampton, United Kingdom.
FAU - Romero, Ignacio A
AU  - Romero IA
AD  - School of Life, Health and Chemical Science, Faculty of Science, Technology, 
      Engineering and Mathematics, The Open University, Milton Keynes, United Kingdom.
FAU - Hawkes, Cheryl A
AU  - Hawkes CA
AD  - School of Life, Health and Chemical Science, Faculty of Science, Technology, 
      Engineering and Mathematics, The Open University, Milton Keynes, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20190704
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC6620643
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - cerebral amyloid angiopathy
OT  - cholinergic
OT  - cortex
OT  - hippocampus
OT  - neurovascular unit
EDAT- 2019/07/25 06:00
MHDA- 2019/07/25 06:01
PMCR- 2019/01/01
CRDT- 2019/07/24 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/06/20 00:00 [accepted]
PHST- 2019/07/24 06:00 [entrez]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2019/07/25 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2019.00172 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2019 Jul 4;11:172. doi: 10.3389/fnagi.2019.00172. 
      eCollection 2019.