Basic Research
Changes of white matter in LDLR knockout hypercholesterolemic rats
Zhao Nana, Guo Hongquan, Xie Yi, Liang Meng, Wang Ming, Wang Yuhui, Liu Guoqing, Hou Huajuan, Ye Ruidong, Liu Xinfeng
Published 2018-01-28
Cite as Int J Cerebrovasc Dis, 2018,26(1): 36-41. DOI: 10.3760/cma.j.issn.1673-4165.2018.01.007
Abstract
ObjectiveTo investigate the difference between histopathological changes of brain white matter in low-density lipoprotein receptor (LDLR) homozygous mutation rats with hypercholesterolemia and wild-type rats.
MethodsThirty LDLR-/- rats and 28 wild-type rats were selected. Plasma cholesterol levels were measured by enzyme-linked immunosorbent assay at 15, 18 and 26 weeks old respectively. The axonal structure of the corpus callosum area was observed by transmission electron microscopy. The myelin basic protein (MBP) of the corpus callosum area was quantitatively analyzed by Western blotting. In addition, at 26 weeks old, the myelin sheaths were stained by fast blue staining. The expression level of MBP in white matter was further detected by immunofluorescence staining, and the morphological changes of glial cells were observed.
ResultsCompared with the wild-type rats, the plasma cholesterol concentration in LDLR-/- rats increased significantly, and it could be as high as 3.3 times at 26 weeks. The results of electron microscopy showed that the LDLR-/- rats had axonal injury at 15 weeks and aggravated gradually over time. At 26 weeks, Western blot analysis of the LDLR-/- rats showed that the MBP expression level of the corpus callosum area decreased significantly. Fast blue staining showed loosening of nerve fibers, diffuse vacuole formation, and myelinated nerve fiber loss in the corpus callosum area. In addition, it was also found that the number of oligodendrocytes in LDLR-/- rats was significantly reduced, and large numbers of astrocytes and microglia were activated.
ConclusionsLDLR-/- rats will have spontaneous hypercholesterolemia. Axonal injury, demyelination, decreased oligodendrocytes, as well as the abnormal activation of astrocytes and microglia are present in the early adult brain white matter area.
Key words:
White Matter; Receptors, LDL; Hypercholesterolemia; Nerve Fibers, Myelinated; Rats, Transgenic; Rats
Contributor Information
Zhao Nana
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Guo Hongquan
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Xie Yi
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Liang Meng
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Wang Ming
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Wang Yuhui
Institute of Cardiovascular Sciences, Key Laboratory of Molecular Cardiology, Ministry of Education, Peking University, Beijing 100083, China
Liu Guoqing
Institute of Cardiovascular Sciences, Key Laboratory of Molecular Cardiology, Ministry of Education, Peking University, Beijing 100083, China
Hou Huajuan
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Ye Ruidong
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
Liu Xinfeng
Department of Neurology, Jingling Hospital, Medical school of Nanjing University, Nanjing 210002, China
