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Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat

View Article: PubMed Central - PubMed

ABSTRACT

Alzheimer’s disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid β oligomers (AβO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AβO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aβ, microglia, and cholinergic neurons. Rats exposed to AβO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aβ was only observed in the corpus callosum surrounding the lateral ventricles. AβO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AβO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AβO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.

No MeSH data available.


Related in: MedlinePlus

Microglia assessment in the hippocampus, basal forebrain and corpus callosum. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with either IBA-1 antibody to label all microglia or Ox-6 antibody to label activated microglia in the hippocampus, basal forebrain and corpus callosum. (A) Photomicrographs of the hippocampus (top two panels) basal forebrain (middle two panels) and corpus callosum (bottom two panels) in in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 21 days post-injection. Scale bars are 100 µm or 1 mm as indicated; (B) quantification using optical densitometry (IBA-1) or activated microglia cell counts (Ox-6) from three adjacent tissue sections per animal. No differences in IBA-1 labelling were observed between AβO-injected and controls across all brain regions. AβO-injected rats had significantly more Ox-6 positive cells within the corpus callosum compared to controls 21 days post-injection. Data presented as group means ± SEM. * indicates statistical significance between AβO-injected and control rats using 2-way ANOVA followed by Tukey’s post-hoc analysis, p < 0.05, n = 5 for each experimental group.
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ijms-17-01390-f004: Microglia assessment in the hippocampus, basal forebrain and corpus callosum. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with either IBA-1 antibody to label all microglia or Ox-6 antibody to label activated microglia in the hippocampus, basal forebrain and corpus callosum. (A) Photomicrographs of the hippocampus (top two panels) basal forebrain (middle two panels) and corpus callosum (bottom two panels) in in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 21 days post-injection. Scale bars are 100 µm or 1 mm as indicated; (B) quantification using optical densitometry (IBA-1) or activated microglia cell counts (Ox-6) from three adjacent tissue sections per animal. No differences in IBA-1 labelling were observed between AβO-injected and controls across all brain regions. AβO-injected rats had significantly more Ox-6 positive cells within the corpus callosum compared to controls 21 days post-injection. Data presented as group means ± SEM. * indicates statistical significance between AβO-injected and control rats using 2-way ANOVA followed by Tukey’s post-hoc analysis, p < 0.05, n = 5 for each experimental group.

Mentions: One of the earliest pathological consequences in the pathogenesis of AD includes an increased microglial response within several brain regions including the cortex, hippocampus, basal forebrain and white matter tracts [39]. To assess microglia activation an antibody specific to activated microglia (Ox-6) along with an antibody that labels all microglia (IBA-1) regardless of activation status was used (Figure 4). No significant differences were observed in either total microglia or activated microglia within the hippocampus or basal forebrain between AβO-injected and controls (Figure 4). However, a significant increase in Ox-6 positive activated microglia was observed in AβO-injected rats at 21 days post-injection within the corpus callosum compared to control rats (Figure 4, control—6.5 ± 1.8 cells/mm2, AβO—14.11 ± 3.40 cells/mm2).


Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat
Microglia assessment in the hippocampus, basal forebrain and corpus callosum. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with either IBA-1 antibody to label all microglia or Ox-6 antibody to label activated microglia in the hippocampus, basal forebrain and corpus callosum. (A) Photomicrographs of the hippocampus (top two panels) basal forebrain (middle two panels) and corpus callosum (bottom two panels) in in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 21 days post-injection. Scale bars are 100 µm or 1 mm as indicated; (B) quantification using optical densitometry (IBA-1) or activated microglia cell counts (Ox-6) from three adjacent tissue sections per animal. No differences in IBA-1 labelling were observed between AβO-injected and controls across all brain regions. AβO-injected rats had significantly more Ox-6 positive cells within the corpus callosum compared to controls 21 days post-injection. Data presented as group means ± SEM. * indicates statistical significance between AβO-injected and control rats using 2-way ANOVA followed by Tukey’s post-hoc analysis, p < 0.05, n = 5 for each experimental group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5037670&req=5

ijms-17-01390-f004: Microglia assessment in the hippocampus, basal forebrain and corpus callosum. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with either IBA-1 antibody to label all microglia or Ox-6 antibody to label activated microglia in the hippocampus, basal forebrain and corpus callosum. (A) Photomicrographs of the hippocampus (top two panels) basal forebrain (middle two panels) and corpus callosum (bottom two panels) in in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 21 days post-injection. Scale bars are 100 µm or 1 mm as indicated; (B) quantification using optical densitometry (IBA-1) or activated microglia cell counts (Ox-6) from three adjacent tissue sections per animal. No differences in IBA-1 labelling were observed between AβO-injected and controls across all brain regions. AβO-injected rats had significantly more Ox-6 positive cells within the corpus callosum compared to controls 21 days post-injection. Data presented as group means ± SEM. * indicates statistical significance between AβO-injected and control rats using 2-way ANOVA followed by Tukey’s post-hoc analysis, p < 0.05, n = 5 for each experimental group.
Mentions: One of the earliest pathological consequences in the pathogenesis of AD includes an increased microglial response within several brain regions including the cortex, hippocampus, basal forebrain and white matter tracts [39]. To assess microglia activation an antibody specific to activated microglia (Ox-6) along with an antibody that labels all microglia (IBA-1) regardless of activation status was used (Figure 4). No significant differences were observed in either total microglia or activated microglia within the hippocampus or basal forebrain between AβO-injected and controls (Figure 4). However, a significant increase in Ox-6 positive activated microglia was observed in AβO-injected rats at 21 days post-injection within the corpus callosum compared to control rats (Figure 4, control—6.5 ± 1.8 cells/mm2, AβO—14.11 ± 3.40 cells/mm2).

View Article: PubMed Central - PubMed

ABSTRACT

Alzheimer&rsquo;s disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid &beta; oligomers (A&beta;O) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to A&beta;O via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for A&beta;, microglia, and cholinergic neurons. Rats exposed to A&beta;O showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for A&beta; was only observed in the corpus callosum surrounding the lateral ventricles. A&beta;O exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to A&beta;O resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to A&beta;O in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.

No MeSH data available.


Related in: MedlinePlus