10 29

Cited 0 times in

Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model

Authors
 Jaewoo Shin  ;  Chanho Kong  ;  Jihyeon Lee  ;  Bo Young Choi  ;  Jiyeon Sim  ;  Chin Su Koh  ;  Minkyung Park  ;  Young Cheol Na  ;  Sang Won Suh  ;  Won Seok Chang  ;  Jin Woo Chang 
Citation
 Alzheimer's Research & Therapy, Vol.11(1) : 110, 2019 
Journal Title
 Alzheimer's Research & Therapy 
Issue Date
2019
Keywords
Alzheimer’s disease ; Brain-derived neurotrophic factor ; Dementia ; Hippocampus ; Microbubbles ; Neuropathology ; Rats, Sprague-Dawley ; Sonication
Abstract
BACKGROUND: The persistence of adult hippocampal neurogenesis (AHN) is sharply decreased in Alzheimer's disease (AD). The neuropathologies of AD include the presence of amyloid-β deposition in plaques, tau hyperphosphorylation in neurofibrillary tangles, and cholinergic system degeneration. The focused ultrasound (FUS)-mediated blood-brain barrier opening modulates tau hyperphosphorylation, the accumulation of amyloid-β proteins, and increases in AHN. However, it remains unclear whether FUS can modulate AHN in cholinergic-deficient conditions. In this study, we investigated the effect of FUS on AHN in a cholinergic degeneration rat model of dementia. METHODS: Adult male Sprague-Dawley rats (n = 48; 200-250 g) were divided into control (phosphate-buffered saline injection), 192 IgG-saporin (SAP), and SAP+FUS groups; in the two latter groups, SAP was injected bilaterally into the lateral ventricle. We applied FUS to the bilateral hippocampus with microbubbles. Immunohistochemistry, enzyme-linked immunosorbent assay, immunoblotting, 5-bromo-2'-deoxyuridine labeling, an acetylcholinesterase assay, and the Morris water maze test were performed to assess choline acetyltransferase, acetylcholinesterase activity, brain-derived neurotrophic factor expression, neural proliferation, and spatial memory, respectively. Statistical significance of differences in between groups was calculated using one-way and two-way analyses of variance followed by Tukey's multiple comparison test to determine the individual and interactive effects of FUS on immunochemistry and behavioral analysis. P < 0.05 was considered significant. RESULTS: Cholinergic degeneration in rats significantly decreased the number of choline acetyltransferase neurons (P < 0.05) in the basal forebrain, as well as AHN and spatial memory function. Rats that underwent FUS-mediated brain-blood barrier opening exhibited significant increases in brain-derived neurotrophic factor (BDNF; P < 0.05), early growth response protein 1 (EGR1) (P < 0.01), AHN (P < 0.01), and acetylcholinesterase activity in the frontal cortex (P < 0.05) and hippocampus (P < 0.01) and crossing over (P < 0.01) the platform in the Morris water maze relative to the SAP group after sonication. CONCLUSIONS: FUS treatment increased AHN and improved spatial memory. This improvement was mediated by increased hippocampal BDNF and EGR1. FUS treatment may also restore AHN and protect against neurodegeneration, providing a potentially powerful therapeutic strategy for AD.
Files in This Item:
T201905681.pdf Download
DOI
10.1186/s13195-019-0569-x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Koh, Chin Su(고진수)
Kong, Chanho(공찬호)
Shin, Jaewoo(신재우) ORCID logo https://orcid.org/0000-0002-6335-1292
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174832
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse