Chronic cerebral hypoperfusion induces memory deficits and facilitates Aβ generation in C57BL/6J mice
| Autor: | Lingxi Wang, Ye‐Hong Du, Shifang Luo, Kejian Wang, Guiqiong He, Ge Xu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system Pathology medicine.medical_specialty Time Factors Enzyme-Linked Immunosorbent Assay Nerve Tissue Proteins Brain Ischemia Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine GAP-43 Protein Developmental Neuroscience Microscopy Electron Transmission Tubulin medicine Extracellular Dementia Animals Aspartic Acid Endopeptidases Cyclin D1 Cognitive decline Maze Learning Pathological Aquaporin 4 Memory Disorders Amyloid beta-Peptides Membrane Proteins Cognition medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Neurology Cerebral blood flow Synapses Amyloid Precursor Protein Secretases Psychology Neuroscience Disks Large Homolog 4 Protein Guanylate Kinases 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Experimental neurology. 283 |
| ISSN: | 1090-2430 |
| Popis: | Alzheimer's disease (AD) is the most common type of dementia frequently responsible for cognitive decline in the elderly. The etiology and molecular mechanism of AD pathogenesis remain inconclusive. Aging and vascular factors are important independent causes and contributors to sporadic AD. Clinical imaging studies showed that cerebral blood flow decreases before cognitive impairment in patients with AD. To investigate the effect of chronic cerebral hypoperfusion (CCH) on cognitive impairment and morphological features, we developed a new manner of CCH mouse model by narrowing bilateral common carotid arteries. Mice started to manifest spatial memory deficits 1month after the surgery and exhibited behavioral changes in a time-dependent manner. Mice also presented memory deficits accompanied with morphological changes at the neuronal and synaptic levels. CCH damaged the normal neuronal morphology and significantly reduced the expression level of PSD95. CCH activated astrocytes, increased the co-expression of GFAP and AQP4, and destroyed the blood-brain barrier (BBB). Furthermore, CCH facilitated intracellular and extracellular Aβ deposition by up-regulating γ-secretase and β-secretase levels. Our results showed good reproducibility of post-CCH pathological processes, which are characterized by neuronal apoptosis, axonal abnormalities, glial activation, BBB damage, amyloid deposition, and cognitive dysfunction; these processes may be used to decipher the complex interplay and pathological process between CCH and AD. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction and AD. |
| Databáze: | OpenAIRE |
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