Age-related changes in cerebral blood vessels influencing cognitive ability in SAMP8 mouse models of AD

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Author:
ZHANG Xue-zhu(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
LIU Xu(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
LIU Jin-feng(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
NIE Kun(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
JIA Yu-jie(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
YU Jian-chun(Institute of Acupuncture and Moxibustion, First Affiliated Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China)
Journal Title:
Chinese Journal of Neuromedicine
Issue:
Volume 11, Issue 09, 2012
DOI:
10.3760/cma.j.issn.1671-8925.2012.09.004
Key Word:
Alzheimer's disease;Cerebral blood flow;Blood brain barrier;Brain glucose metabolism;Cognition

Abstract: Objective To explore the influence of age-related changes in the cerebral blood vessels (cerebral blood flow,blood-brain barrier integrity,and level of glucose transporter [GLUT]) in cognitive ability of SAMP8 mouse models of AD. Methods Ten SAMP8 mice and 10 homologous anti-senescence accelerated mice R1 (SAMR1) were chosen in our study; spatial learning and memory abilities of these mice were assessed using Morris water maze; cerebral blood flow was determined by laser Doppler flowmeter; blood-brain barrier (BBB) permeability was examined by fluorescence spectrophotometer; and expressions of GLUT1 and GLUT3 were determined using Western blotting.Results The cognitive abilities of SAMP8 mice damaged apparently even at 4 months of age as compared with those of SAMR1 mice, showing rigid thinking pattern and slow learning process in their Morris water maze test. With increasing of age, much obvious decrement in cerebral blood flow and severe BBB leakage was observed in SAMP8 mice; moreover, alterations in GLUT1 and GLUT3 expressions in the cortex and hippocampus of SAMP8 mice were observed. The cerebral blood flow,BBB integrity,and expressions of GLUT1 and GLUT3 were significantly affected by age and strain,and closely associated with cognitive abilities. Conclusion The alterations in cerebral blood flow and energy failure induced by aging and vascular insults are the reasons for neuron dysfunction and cognitive impairment in mice models of AD.

  • [1]Yoshiura T,Hiwatashi A,Noguchi T,et al.Arterial spin labelling at 3-T MR imaging for detection of individuals with Alzheimer's disease[J].Eur Radiol,2009,19(12):2819-2825.
  • [2]Ruitenberg A,den Heijer T,Bakker SL,et al. Cerebral hypoperfusion and clinical onset of dementia:the Rotterdam Study[J].Ann Neurol,2005,57(6):789-794.
  • [3]Staffen W,Bergmann J,Schonauer U,et al.Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer's type: a semiquantitative and automated evaluation[J].Eur J Nucl Med Mol Imaging,2009,36(5):801-810.
  • [4]Schonknecht OD,Hunt A,Toro P,et al.Bihemispheric cerebral FDG PET correlates of cognitive dysfunction as assessed by the CERAD in Alzheimer's disease[J].Clin EEG Neurosci,2011,42(2):71-76.
  • [5]Scholl M,Almkvist O,Bogdanovic N,et al.Time course of glucose metabolism in relation to cognitive performance and postmortem neuropathology in Met146Val PSEN1 mutation carriers [J]. J Alzheimers Dis,2011,24(3):495-506.
  • [6]Mosconi L,De Santi S,Li J,et al.Hippocampal hypometabolism predicts cognitive decline from normal aging[J].Neurobiol Aging,2008,29(5):676-692.
  • [7]Mosconi L,De Santi S,Brys M,et al.Hypometabolism and altered cerebrospinal fluid markers in normal apolipoprotein E E4 carriers with subjective memory complaints[J].Biol Psychiatry,2008,63(6):609-618.
  • [8]Samuraki M,Matsunari I,Chen WP,et al.Partial volume effect-corrected FDG PET and grey matter volume loss in patients with mild Alzheimer's disease[J].Eur J Nucl Med Mol Imaging,2007,34(10):1658-1669.
  • [9]Morley JE,Kumar VB,Bernardo AE,et al.Beta-amyloid precursor polypeptide in SAMP8 mice affects learning and memory [J].Peptides,2000,21(12):1761-1767.
  • [10]崔冉亮,戌凯,吕朴,等.四氧嘧啶脑室内注射对小鼠学习记忆的影响[J].中华神经医学杂志,2011,10(4):346-350.
  • [11]Weidensteiner C,Metzger F,Bruns A,et al.Cortical hypoperfusion in the B6.PS2APP mouse model for Alzheimer's disease:comprehensive phenotyping of vascular and tissular parameters by MRI[J].Magn Reson Med,2009,62(1):35-45.
  • [12]Mosconi L,Mistur R,Switalski R,et al.FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease [J]. Eur J Nucl Med Mol Imaging,2009,36(5):811-822.
  • [13]Cunnane S,Nugent S,Roy M,et al.,Brain fuel metabolism,aging,and Alzheimer's disease[J].Nutrition,2011,27(1):3-20.
  • [14]Mosconi L,Tsui WH,Rusinek H,et al.Quantitation,regional vulnerability and kinetic modeling of brain glucose metabolism in mild Alzheimer' s disease[J].Eur J Nucl Med Mol Imaging,2007,34(9):1467-1479.
  • [15]Bowman GL,Kaye JA,Moore M,et al.Blood-brain barrier impairment in Alzheimer disease: stability and functional significance[J].Neurology,2007,68(21):1809-1814.
  • [16]Ujiie M,Dickstein DL,Carlow DA,et al.Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model[J].Microcirculation,2003,10(6):463-470.
  • [17]Liu Y,Liu F,Grundke-Iqbal I,et al.Brain glucose transporters,O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease[J].J Neurochem,2009,111 (1):242-249.
  • [18]Vemula S,Roder KE,Yang T,et al.A functional role for sodium-dependent glucose transport across the blood-brain barrier during oxygen glucose deprivation [J]. J Pharmacol Exp Ther,2009,328(2):487-495.
  • [19]de la Torre JC.Pathophysiology of neuronal energy crisis in Alzheimer's disease[J].Neurodegener Dis,2008,5(3-4):126-132.
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