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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Differences in amyloid-β and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic
Hiroshi Kagusa1, Izumi Yamaguchi1, Kenji Shono1
1Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Background:
Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-β (Aβ), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear.
Objectives:
To test our hypothesis that Aβ, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied.
Methods:
Seven-week-old C57BL/6 male mice were injected with 15 μL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aβ, tau, and p-tau were assessed immunohistochemically over time.
Results:
On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aβ deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aβ. Deposits of Aβ, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aβ and tau/p-tau.
Conclusion:
Deposition and regulation differ between Aβ and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.
Insights
Cerebral microbleeds from TBI show distinct amyloid-beta and tau/p-tau accumulation patterns. These findings suggest separate pathological mechanisms contributing to cognitive decline after traumatic brain injury.
Area of Science:
- Neuroscience
- Neuropathology
- Traumatic Brain Injury Research
Background:
- Cerebral microbleeds (CMBs) following traumatic brain injury (TBI) are linked to cognitive impairment.
- Pathophysiological mechanisms may involve inflammation and the accumulation of amyloid-beta (Aβ), tau, and phosphorylated tau (p-tau).
- The precise relationships between CMBs and these specific protein pathologies remain unclear.
Purpose of the Study:
- To investigate the distinct accumulation and regulation of Aβ, tau, and p-tau in a mouse model of TBI-induced CMBs.
- To test the hypothesis that these proteins are regulated independently in response to simulated microbleeds.
Main Methods:
- Induction of CMBs in mice by injecting autologous blood into the frontal lobe.
- Immunohistochemical assessment of Aβ, tau, and p-tau expression and deposition over time.
- Analysis of inflammatory markers (Iba-1, S100B) and macrophage activity (CD163).
Main Results:
- Increased inflammatory cells (Iba-1+, S100B+) were observed post-injection.
- Aβ deposition peaked early (days 3-14) and normalized by day 28.
- Tau/p-tau deposition increased later (days 14-28) and exhibited different distribution patterns.
- Aβ, but not tau/p-tau, was phagocytosed by activated macrophages.
Conclusions:
- Amyloid-beta and tau/p-tau exhibit differential deposition and regulatory mechanisms following TBI-induced CMBs.
- These distinct pathological pathways warrant further investigation to understand their contribution to cognitive deficits and neurodegeneration.
