Limits...
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

Behavioural assessment using the Morris water maze (A–C) and open field tasks (D–F). (A) Latency to reach platform was measured on post-surgical days 8–11 to assess initial learning of the task. AβO-injected rats took significantly longer to reach the platform on day 9 compared to control rats; (B) probe trials were performed on days 12 and 19 to assess memory. AβO-injected rats took significantly longer to reach the platform on day 12 compared to controls; (C) mean swim time indicated no differences in swim speed between AβO-injected and control rats; (D) AβO-injected rats showed significantly less ambulatory time compared to controls in the open field task; (E) AβO-injected rats spent significantly less time in the central zone compared to control rats; (F) no differences in motor ability detected using vertical counts between AβO-injected and control rats. 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 (A,B) and a 2-tailed students t-test (D,F), p < 0.05, n = 8 for each experimental group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037670&req=5

ijms-17-01390-f001: Behavioural assessment using the Morris water maze (A–C) and open field tasks (D–F). (A) Latency to reach platform was measured on post-surgical days 8–11 to assess initial learning of the task. AβO-injected rats took significantly longer to reach the platform on day 9 compared to control rats; (B) probe trials were performed on days 12 and 19 to assess memory. AβO-injected rats took significantly longer to reach the platform on day 12 compared to controls; (C) mean swim time indicated no differences in swim speed between AβO-injected and control rats; (D) AβO-injected rats showed significantly less ambulatory time compared to controls in the open field task; (E) AβO-injected rats spent significantly less time in the central zone compared to control rats; (F) no differences in motor ability detected using vertical counts between AβO-injected and control rats. 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 (A,B) and a 2-tailed students t-test (D,F), p < 0.05, n = 8 for each experimental group.

Mentions: The Morris water maze task was used to determine whether exposure to AβO in rats would result in deficits in spatial learning and memory (Figure 1A–C). During the spatial learning phase, both the AβO-injected and control (PBS-injected) rats were able to successfully learn the location of the hidden platform, however the AβO-injected rats performed poorer, as indicated by a longer latency to reach the platform (control—17.35 ± 1.86 s, AβO—29.06 ± 5.40 s) on day 9 compared to control rats (Figure 1A). Probe trials at post-surgery day 12 and 19 was performed to assess any effects on short- or long-term spatial memory respectively (Figure 1B). AβO-injected rats took significantly longer to reach the platform on probe trial day 12 than the control rats (control—6.81 ± 0.85 s, AβO—18.01 ± 4.71 s). No differences in latency to reach the platform were observed by probe trial day 19. To insure that the differences in task performance wasn’t caused by motor, or other physiological deficits unrelated to AβO exposure, cued learning trials were performed on days 20 and 21 post-surgery (Figure 1C). No differences in swim speed were detected between AβO- and PBS-injected rats.


Assessing the Effects of Acute Amyloid β Oligomer Exposure in the Rat
Behavioural assessment using the Morris water maze (A–C) and open field tasks (D–F). (A) Latency to reach platform was measured on post-surgical days 8–11 to assess initial learning of the task. AβO-injected rats took significantly longer to reach the platform on day 9 compared to control rats; (B) probe trials were performed on days 12 and 19 to assess memory. AβO-injected rats took significantly longer to reach the platform on day 12 compared to controls; (C) mean swim time indicated no differences in swim speed between AβO-injected and control rats; (D) AβO-injected rats showed significantly less ambulatory time compared to controls in the open field task; (E) AβO-injected rats spent significantly less time in the central zone compared to control rats; (F) no differences in motor ability detected using vertical counts between AβO-injected and control rats. 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 (A,B) and a 2-tailed students t-test (D,F), p < 0.05, n = 8 for each experimental group.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01390-f001: Behavioural assessment using the Morris water maze (A–C) and open field tasks (D–F). (A) Latency to reach platform was measured on post-surgical days 8–11 to assess initial learning of the task. AβO-injected rats took significantly longer to reach the platform on day 9 compared to control rats; (B) probe trials were performed on days 12 and 19 to assess memory. AβO-injected rats took significantly longer to reach the platform on day 12 compared to controls; (C) mean swim time indicated no differences in swim speed between AβO-injected and control rats; (D) AβO-injected rats showed significantly less ambulatory time compared to controls in the open field task; (E) AβO-injected rats spent significantly less time in the central zone compared to control rats; (F) no differences in motor ability detected using vertical counts between AβO-injected and control rats. 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 (A,B) and a 2-tailed students t-test (D,F), p < 0.05, n = 8 for each experimental group.
Mentions: The Morris water maze task was used to determine whether exposure to AβO in rats would result in deficits in spatial learning and memory (Figure 1A–C). During the spatial learning phase, both the AβO-injected and control (PBS-injected) rats were able to successfully learn the location of the hidden platform, however the AβO-injected rats performed poorer, as indicated by a longer latency to reach the platform (control—17.35 ± 1.86 s, AβO—29.06 ± 5.40 s) on day 9 compared to control rats (Figure 1A). Probe trials at post-surgery day 12 and 19 was performed to assess any effects on short- or long-term spatial memory respectively (Figure 1B). AβO-injected rats took significantly longer to reach the platform on probe trial day 12 than the control rats (control—6.81 ± 0.85 s, AβO—18.01 ± 4.71 s). No differences in latency to reach the platform were observed by probe trial day 19. To insure that the differences in task performance wasn’t caused by motor, or other physiological deficits unrelated to AβO exposure, cued learning trials were performed on days 20 and 21 post-surgery (Figure 1C). No differences in swim speed were detected between AβO- and PBS-injected rats.

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