Share:
Share this content in WeChat
X
Original Article
Quantitative research for metabolites by 9.4 T 1H-MRS in hippocampus of Alzheimer's disease mice
PANG Li  YAO Jian-li  CHEN Yao-wen  LI Hai-hong  YOU Ke-zeng  XU Zhi-feng  WU Ren-hua 

DOI:10.3969/j.issn.1674-8034.2014.04.013.


[Abstract] Objective: To study Alzheimer's disease mice caused by the D-galactose and NaNO2, observe the alteration of hippocampal metabolites using in vitro 9.4 T high resolution magnetic resonance spectroscopy.Materials and Methods: Twenty kunming mice were randomly divided into two groups, model group and control group. Female to male ratio was 1:1. The mice in the model group were subcutaneouly injected with D-galactose 120 mg/(kg.d), NaNO2 90 mg/(kg.d) for 60 days and the control group with oral saline. 24 hours later after Morris water maze test, all mice were sacrificed and the right hippocampus were dissected for 1H-MRS examination. Data were collected using in vitro 9.4 T high resolution magnetic resonance spectrometer. Spectra were processed using XWINNMR and MestRe-c 4.3. Compared with the left side, HE and Bielschowsky silver impregnation and congored coloration were employed to detect and confirm the change of brain cells.Results: Good 1H-MR spectra of perchloric acid extract from hippocampus tissue of mice were obtained. The conventional metabolites were detected and assigned. Mean concentrations of metabolites in control group and model group were, NAA: (43.63±7.67) mmol/L and (34.66±6.79) mmol/L. Cho: (53.09±4.32) mmol/L and (48.62±7.92) mmol/L. Glu: (26.87±5.46) mmol/L and (14.87±2.68) mmol/L. mI: (45.93±6.73) mmol/L and (74.09±8.09) mmol/L, the differences of two groups were statistically significance (P<0.05). Results of Morris water maze behavior examination were as: the escape lateney and the movement distance percentage and time percentage were significant difference between control group and model group (P<0.05). The neurons in control group were intact and arrange tightly. In the model, pyramidal neurons either presented a densely stained shrunken appearance with minimal cytoplasm or had disappeared. Bielschowsky silver impregnation, many neurofibrillary tangles were found, and neuropil threads are stained in model group. Congored coloration result: in the cerebral cortex and hippocampal fields, orange amylaceous aggradation can be seen.Conclusions: D-galactose and NaNO2 can cause the mice induce Alzheimer's disease in vivo. High resolution 1H-MRS in vitro can detect diversified metabolism. In the model group the hippocampal concentrations of NAA, Cho, Glu are decrease. The changing trend for mI is increase.
[Keywords] Alzheimer disease;Hippocampus;Metabolism;Magnetic resonance imaging;Animals laboratory

PANG Li Department of Radiology, the Second Affiliated Hospital, Medical of Shantou University, Shantou 515041, China; Department of Radiology, Changping Hospital of Integrated Chinese and Western Medicine, Beijing 102208, China

YAO Jian-li Department of Radiology, the Second Affiliated Hospital, Medical of Shantou University, Shantou 515041, China

CHEN Yao-wen Central Laboratory, Shantou University, Shantou 515063, China

LI Hai-hong The Mental Health Center, Medical College, Shantou University, Shantou 515063, China

YOU Ke-zeng Department of Radiology, the Second Affiliated Hospital, Medical of Shantou University, Shantou 515041, China

XU Zhi-feng Department of Radiology, the Second Affiliated Hospital, Medical of Shantou University, Shantou 515041, China

WU Ren-hua* Department of Radiology, the Second Affiliated Hospital, Medical of Shantou University, Shantou 515041, China

*Correspondence to: Wu RH, E-mail: cjr.wurenhua@vip.163.com

Conflicts of interest   None.

Received  2014-02-11
Accepted  2014-04-20
DOI: 10.3969/j.issn.1674-8034.2014.04.013
DOI:10.3969/j.issn.1674-8034.2014.04.013.

[1]
Zaven S, Hachaturian K. Diagnosis of Alzheimer’s disease. Arch Neurol, 1985, 42(11): 1097-1105.
[2]
Dickson DW. Neuropathological diagnosis of Alzheimer’s disease: a perspective from longitudinal clinic pathological studies. Neurobiol Aging, 1997, 18(4Supp l): S21-26.
[3]
医学实验动物管理实施细则.中国卫生法制, 1998, 3(34): 39-40.
[4]
Fang F, Liu G. A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. Basic Clin Pharmacol Toxico, 2007, 101(6): 447-454.
[5]
Serres S, Bezancon E, Franconi JM, et al. Exvivo analysis of lactate and glucose metabolism in the rat brain under different states of depressed activity. J Biol Chem, 2004, 279(46): 47881-47889.
[6]
Ferrer I, Martí E, López E, et al. NF-kB immunoreactivity is observed in association with beta A4 diffuse plaques in patients with Alzheimer’s disease. Neuropathol Appl Neurobiol, 1998, 24(4): 271-277.
[7]
Bertoni-Freddari C, Giuli C, Pieric C, et al. Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging. Brain Res, 1986, 366(1-2): 187-192.
[8]
Michaelis T, Merboldt KD, Bruhn H, et al. Absolute concentrations of metabolites in the adult human brain in vivo: quantification of localized proton MR spectra. Radiology, 1993, 187(1): 219-227.
[9]
Kantarci K, Reynolds G, Petersen RC, et al. Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: comparison of 1.5 T and 3 T. AJNR Am J Neuroradiol, 2003, 24(5): 843-849.
[10]
Moats RA, Emst T, Shonk TK, et al. Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med, 1994, 32(1): 110-115.
[11]
Frick Km, Steams NA, Pan JY, et al. Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice. Learn Mem, 2003, 10(3): 187-198.
[12]
Bates TE, Stranqward M, Keelan J, et al. Inhibition of N-acetylaspartate production: implications for 1H MRS studies in vivo. Neuroreport, 1996, 7(8): 1397-1400.
[13]
De Stefano N, Mortilla M, Federico A. Proton magnetic resonance spectroscopy of the brain in dementia. Ital J Neurol Sci, 1999, 20(5Suppl): S258-264.
[14]
Shiino A, Matsuda M, Morikawa S, et al. Proton magnetic resonance spectroscopy with dementia. Surg Neurol, 1993, 39(2): 143-147.
[15]
Emst T, Chang L, Melchor R, et al. Frontotemporal dementia and early Alzheimer disease: differentiation with frontal lobe H-1 MR spectroscopy. Radiology, 1997, 203(3): 829-836.
[16]
Pfeuffer J, Tkac I, Provencher SW, et al. Toward an in vivo neurochemical profile: quantification of 18 metabolities in short-echo-time (1) H MRS spectra of rat brain. J Magn Reson, 1999, 141(1): 104-120.
[17]
张超,穆学涛,王宏. ADDTI早期诊断的研究进展.磁共振成像, 2013, 4(5): 394-397.

PREV Dynamic MRI research of EPCs tracing rat glioma
NEXT How to optimize breast MR imaging practices and techniques
  



Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn