Disruption of neuronal-glial-vascular units in the hippocampus of ovariectomized mice injected with D-galactose.
Neuronal-glial-vascular units now have been regarded as the basic functional elements of the CNS; however, their pathophysiological changes in the neurodegenerative condition are poorly defined. Herein we addressed these issues in the hippocampus of an Alzheimer's disease mouse model which was established by ovariectomy and then followed with 8 weeks of d-galactose injection. Immunolocalization of glial fibrillary acidic protein showed that reactive astrogliosis destroyed astrocytic domain organization in the hippocampus of model mice. Electron microscopy further demonstrated microarchitectural damage of neuronal-glial units and gliovascular units in the CA1 stratum radiatum of model group. Moreover, model mice had decreased expressions of glutamate transporter 1, glutamate/aspartate transporter, glutamine synthetase and connexin 43, but an increased expression of water channel protein aquaporin-4 in the hippocampus as revealed by immunohistochemistry and immunoblotting analysis. These results highlight that disruptions in structural integrity of the neuronal-glial-vascular units and associated functions including glutamate clearance, water transport and astrocyte syncytium contribute to the neurodegeneration induced by long-term ovarian hormone deprivation and systemic d-galactose exposure.
Liu
L
L
Jiangsu Key Laboratory of Neurodegeneration, Department of Anatomy, Histology and Pharmacology of Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu Province 210029, PR China.
Su
Y
Y
Yang
W
W
Xiao
M
M
Gao
J
J
Hu
G
G
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis; D001692:Biological Transport; D002450:Cell Communication; D018031:Connexin 43 / Q000096:biosynthesis; D004195:Disease Models, Animal; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis; D005690:Galactose; D015726:Giant Cells / Q000648:ultrastructure; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D055806:Microvessels / Q000378:metabolism / Q000648:ultrastructure; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D010052:Ovariectomy; D014867:Water / Q000378:metabolism
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D018031:Connexin 43; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; C543076:GJA1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; C493393:Slc1a3 protein, mouse; D014867:Water; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase; D005690:Galactose