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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

Immunolabelling for Aβ deposition within the corpus callosum and cingulate gyrus. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the Aβ4G8 antibody with an epitope against the 17–24 amino acid sequence of the Aβ peptide. (A) Photomicrographs of the corpus callosum and cingulate gyrus in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, 3, 7 and 21 days post-injection. Bottom panels are higher magnification images of the panels immediately above (indicated by the box). Scale bars are 200 or 100 µm as indicated; (B) quantification using optical densitometry from three adjacent tissue sections per animal. AβO-injected rats had significantly more Aβ labelling in the corpus callosum and cingulate gyrus compared to controls at days 1 and 3 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-f002: Immunolabelling for Aβ deposition within the corpus callosum and cingulate gyrus. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the Aβ4G8 antibody with an epitope against the 17–24 amino acid sequence of the Aβ peptide. (A) Photomicrographs of the corpus callosum and cingulate gyrus in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, 3, 7 and 21 days post-injection. Bottom panels are higher magnification images of the panels immediately above (indicated by the box). Scale bars are 200 or 100 µm as indicated; (B) quantification using optical densitometry from three adjacent tissue sections per animal. AβO-injected rats had significantly more Aβ labelling in the corpus callosum and cingulate gyrus compared to controls at days 1 and 3 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: We next investigated whether or not the AβO injections would result in Aβ deposition in the brain as well as to identify where the deposition may occur, and for how long it might in the brain. To identify Aβ deposition, immunohistochemical stains were done with Aβ4G8 antibody, which recognizes the 17–24 amino acid sequence of the Aβ protein (Figure 2). There was only one region within the brain that demonstrated positive Aβ4G8 labelling—the corpus callosum and cingulate gyrus adjacent to the injection sites, but remote from the injection sites themselves. In this region a transient increase in Aβ4G8 labelling was observed in AβO-injected rats compared to controls. Quantification of Aβ4G8 labelling revealed a significant increase in signal both at 1 and 3 days post-injection compared to controls (Figure 1B). By 7 days post-injection there were no differences in Aβ4G8 labelling between AβO-injected rats and controls (Figure 1B) indicating that any Aβ deposition caused by the AβO-injection was likely cleared from the brain parenchyma.


Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat
Immunolabelling for Aβ deposition within the corpus callosum and cingulate gyrus. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the Aβ4G8 antibody with an epitope against the 17–24 amino acid sequence of the Aβ peptide. (A) Photomicrographs of the corpus callosum and cingulate gyrus in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, 3, 7 and 21 days post-injection. Bottom panels are higher magnification images of the panels immediately above (indicated by the box). Scale bars are 200 or 100 µm as indicated; (B) quantification using optical densitometry from three adjacent tissue sections per animal. AβO-injected rats had significantly more Aβ labelling in the corpus callosum and cingulate gyrus compared to controls at days 1 and 3 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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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037670&req=5

ijms-17-01390-f002: Immunolabelling for Aβ deposition within the corpus callosum and cingulate gyrus. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the Aβ4G8 antibody with an epitope against the 17–24 amino acid sequence of the Aβ peptide. (A) Photomicrographs of the corpus callosum and cingulate gyrus in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, 3, 7 and 21 days post-injection. Bottom panels are higher magnification images of the panels immediately above (indicated by the box). Scale bars are 200 or 100 µm as indicated; (B) quantification using optical densitometry from three adjacent tissue sections per animal. AβO-injected rats had significantly more Aβ labelling in the corpus callosum and cingulate gyrus compared to controls at days 1 and 3 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: We next investigated whether or not the AβO injections would result in Aβ deposition in the brain as well as to identify where the deposition may occur, and for how long it might in the brain. To identify Aβ deposition, immunohistochemical stains were done with Aβ4G8 antibody, which recognizes the 17–24 amino acid sequence of the Aβ protein (Figure 2). There was only one region within the brain that demonstrated positive Aβ4G8 labelling—the corpus callosum and cingulate gyrus adjacent to the injection sites, but remote from the injection sites themselves. In this region a transient increase in Aβ4G8 labelling was observed in AβO-injected rats compared to controls. Quantification of Aβ4G8 labelling revealed a significant increase in signal both at 1 and 3 days post-injection compared to controls (Figure 1B). By 7 days post-injection there were no differences in Aβ4G8 labelling between AβO-injected rats and controls (Figure 1B) indicating that any Aβ deposition caused by the AβO-injection was likely cleared from the brain parenchyma.

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