Selective neurodegeneration of the hippocampus caused by chronic cerebral hypoperfusion: F-18 FDG PET study in rats

• Published in: PloS one 2022-02, Vol.17 (2), p.e0262224-e0262224
• Main Authors: Lee, Jung-In, Lim, Ji Sun, Hong, Jeong-Ho, Kim, Shin, Lee, Sang-Woo, Ji, Hyun Dong, Won, Kyoung Sook, Song, Bong-Il, Kim, Hae Won
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid; Amyloid beta-Peptides - metabolism; Analysis; Animal cognition; Animals; Arteries; Biology and Life Sciences; Brain - diagnostic imaging; Brain research; Care and treatment; Carotid arteries; Carotid Arteries - surgery; Carotid artery; Cognitive ability; Cortex (somatosensory); Dementia; Diagnosis; Disease Models, Animal; Evaluation; Fluorine isotopes; Fluorodeoxyglucose F18 - chemistry; Glucose; Glucose - metabolism; Hippocampus; Hippocampus (Brain); Hippocampus - metabolism; Hospitals; Lasers; Male; Maze Learning; Medicine and Health Sciences; Metabolism; Neurodegeneration; Neurodegenerative diseases; Nuclear medicine; Pathology; Peptide Fragments - metabolism; Positron emission; Positron emission tomography; Radioisotopes; Rats; Rats, Wistar; Regions; Research and Analysis Methods; Rodents; Surgery; Tau protein; tau Proteins - metabolism; Tomography; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0262224

Chronic cerebral hypoperfusion (CCH) is known to induce Alzheimer's disease (AD) pathology, but its mechanism remains unclear. The purpose of this study was to identify the cerebral regions that are affected by CCH, and to evaluate the development of AD pathology in a rat model of CCH. A rat model of CCH was established by bilaterally ligating the common carotid arteries in adult male rats (CCH group). The identical operations were performed on sham rats without arteries ligation (control group). Regional cerebral glucose metabolism was evaluated at 1 and 3 months after bilateral CCA ligation using positron emission tomography with F-18 fluorodeoxyglucose. The expression levels of amyloid β40 (Aβ40), amyloid β42 (Aβ42), and hyperphosphorylated tau were evaluated using western blots at 3 months after the ligation. Cognitive function was evaluated using the Y-maze test at 3 months after the ligation. At 1 month after the ligation, cerebral glucose metabolism in the entorhinal, frontal association, motor, and somatosensory cortices were significantly decreased in the CCH group compared with those in the control group. At 3 months after the ligation, cerebral glucose metabolism was normalized in all regions except for the anterodorsal hippocampus, which was significantly decreased compared with that of the control group. The expression of Aβ42 and the Aβ42/40 ratio were significantly higher in the CCH group than those in the control group. The phosphorylated-tau levels of the hippocampus in the CCH group were significantly lower than those in the control group. Cognitive function was more impaired in the CCH group than that in the control group. Our findings suggest that CCH causes selective neurodegeneration of the anterodorsal hippocampus, which may be a trigger point for the development of AD pathology.