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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 cholinergic neurons within the basal forebrain. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the ChAT antibody that specifically labels cholinergic neurons within the basal forebrain. (A) Photomicrographs of the basal forebrain in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, and 21 days post-injection. Scale bar is 1 mm; (B) Quantification of cholinergic neuron cell counts from three adjacent tissue sections per animal. AβO-injected rats had significantly more ChAT labelling in the basal forebrain 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-f003: Immunolabelling for cholinergic neurons within the basal forebrain. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the ChAT antibody that specifically labels cholinergic neurons within the basal forebrain. (A) Photomicrographs of the basal forebrain in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, and 21 days post-injection. Scale bar is 1 mm; (B) Quantification of cholinergic neuron cell counts from three adjacent tissue sections per animal. AβO-injected rats had significantly more ChAT labelling in the basal forebrain 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: Pathological changes in AD patients include cholinergic neuron loss within the basal forebrain [38]. Specifically, cholinergic neuron loss occurs within the medial septal nucleus (MS) and vertical and horizontal diagonal bands of Broca of the basal forebrain. In this study cholinergic neurons were labelled with choline acetyltransferase (ChAT, Figure 3). By 21 days post-injection AβO-injected rats had significantly less ChAT positive neurons within the basal forebrain compared to controls (Figure 3B, control—26.06 ± 4.31 cells, AβO—14.73 ± 2.38 cells).


Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat
Immunolabelling for cholinergic neurons within the basal forebrain. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the ChAT antibody that specifically labels cholinergic neurons within the basal forebrain. (A) Photomicrographs of the basal forebrain in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, and 21 days post-injection. Scale bar is 1 mm; (B) Quantification of cholinergic neuron cell counts from three adjacent tissue sections per animal. AβO-injected rats had significantly more ChAT labelling in the basal forebrain 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-f003: Immunolabelling for cholinergic neurons within the basal forebrain. Paraformaldehyde perfused rat brains were sectioned at 30 µm and stained with the ChAT antibody that specifically labels cholinergic neurons within the basal forebrain. (A) Photomicrographs of the basal forebrain in coronal rat brain sections from AβO-injected and PBS-injected (control) rats 1, and 21 days post-injection. Scale bar is 1 mm; (B) Quantification of cholinergic neuron cell counts from three adjacent tissue sections per animal. AβO-injected rats had significantly more ChAT labelling in the basal forebrain 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: Pathological changes in AD patients include cholinergic neuron loss within the basal forebrain [38]. Specifically, cholinergic neuron loss occurs within the medial septal nucleus (MS) and vertical and horizontal diagonal bands of Broca of the basal forebrain. In this study cholinergic neurons were labelled with choline acetyltransferase (ChAT, Figure 3). By 21 days post-injection AβO-injected rats had significantly less ChAT positive neurons within the basal forebrain compared to controls (Figure 3B, control—26.06 ± 4.31 cells, AβO—14.73 ± 2.38 cells).

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