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A Rat Model of Alzheimer's Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems.

Petrasek T, Skurlova M, Maleninska K, Vojtechova I, Kristofikova Z, Matuskova H, Sirova J, Vales K, Ripova D, Stuchlik A - Front Aging Neurosci (2016)

Bottom Line: Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function.Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately.Our results show that Samaritan rats(™) exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of SciencesPrague, Czech Republic; National Institute of Mental HealthKlecany, Czech Republic.

ABSTRACT
Alzheimer's disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta42 (Abeta42) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats(™) exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages.

No MeSH data available.


Related in: MedlinePlus

Results from the Morris water maze (MWM). (A) Total distance to reach the platform. In four daily acquisition sessions with a hidden platform in a stable position (d01–d04), Samaritan rats were significantly impaired and their performance did not improve during subsequent sessions, suggesting severe behavioral impairments. The visible platform test showed that both groups had both the motivation and physical ability to reach the platform (the apparent trend towards poorer performance in the Samaritan group was not statistically significant). (B) The probe trial (a single swim without a platform) was performed on the fifth session, after hidden platform training but before visible platform testing. Samaritan rats spent significantly less time in the quadrant that had previously contained the platform, which suggests an impairment of memory or spatial navigation. Their performance was even below the expected random value (15 s), as indicated by the dashed line. Columns in the charts show group means, and SEM is indicated by the error bars. Significant differences between groups or sessions at p < 0.05 as evaluated by a t-test on session-averaged data are indicated by an asterisk (*), n.s. indicates a non-significant result.
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Figure 1: Results from the Morris water maze (MWM). (A) Total distance to reach the platform. In four daily acquisition sessions with a hidden platform in a stable position (d01–d04), Samaritan rats were significantly impaired and their performance did not improve during subsequent sessions, suggesting severe behavioral impairments. The visible platform test showed that both groups had both the motivation and physical ability to reach the platform (the apparent trend towards poorer performance in the Samaritan group was not statistically significant). (B) The probe trial (a single swim without a platform) was performed on the fifth session, after hidden platform training but before visible platform testing. Samaritan rats spent significantly less time in the quadrant that had previously contained the platform, which suggests an impairment of memory or spatial navigation. Their performance was even below the expected random value (15 s), as indicated by the dashed line. Columns in the charts show group means, and SEM is indicated by the error bars. Significant differences between groups or sessions at p < 0.05 as evaluated by a t-test on session-averaged data are indicated by an asterisk (*), n.s. indicates a non-significant result.

Mentions: First we tested rats in the MMW (Figure 1). There were four acquisition sessions in the hidden platform version of the MWM with the platform located in the NE and pseudorandom starting positions. In these sessions, Samaritan rats needed longer paths to locate the platform, indicating that they were impaired. The mixed effects ANOVA (groups × sessions × swims) revealed a significant main effect of group (F(1,13) = 12.62; p < 0.05), sessions (F(3,39) = 4.76; p < 0.05), swims (F(5,65) = 10.57; p < 0.05) and interaction between groups and session (F(3,39) = 4.41; p < 0.05). No other interactions, including a triple interaction between swims, sessions and groups, were detected. The total distance to reach the platform in a particular session is illustrated in Figure 1A-left; though individual swims are not depicted, the total distance decreased in both groups for subsequent swims each day.


A Rat Model of Alzheimer's Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems.

Petrasek T, Skurlova M, Maleninska K, Vojtechova I, Kristofikova Z, Matuskova H, Sirova J, Vales K, Ripova D, Stuchlik A - Front Aging Neurosci (2016)

Results from the Morris water maze (MWM). (A) Total distance to reach the platform. In four daily acquisition sessions with a hidden platform in a stable position (d01–d04), Samaritan rats were significantly impaired and their performance did not improve during subsequent sessions, suggesting severe behavioral impairments. The visible platform test showed that both groups had both the motivation and physical ability to reach the platform (the apparent trend towards poorer performance in the Samaritan group was not statistically significant). (B) The probe trial (a single swim without a platform) was performed on the fifth session, after hidden platform training but before visible platform testing. Samaritan rats spent significantly less time in the quadrant that had previously contained the platform, which suggests an impairment of memory or spatial navigation. Their performance was even below the expected random value (15 s), as indicated by the dashed line. Columns in the charts show group means, and SEM is indicated by the error bars. Significant differences between groups or sessions at p < 0.05 as evaluated by a t-test on session-averaged data are indicated by an asterisk (*), n.s. indicates a non-significant result.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837344&req=5

Figure 1: Results from the Morris water maze (MWM). (A) Total distance to reach the platform. In four daily acquisition sessions with a hidden platform in a stable position (d01–d04), Samaritan rats were significantly impaired and their performance did not improve during subsequent sessions, suggesting severe behavioral impairments. The visible platform test showed that both groups had both the motivation and physical ability to reach the platform (the apparent trend towards poorer performance in the Samaritan group was not statistically significant). (B) The probe trial (a single swim without a platform) was performed on the fifth session, after hidden platform training but before visible platform testing. Samaritan rats spent significantly less time in the quadrant that had previously contained the platform, which suggests an impairment of memory or spatial navigation. Their performance was even below the expected random value (15 s), as indicated by the dashed line. Columns in the charts show group means, and SEM is indicated by the error bars. Significant differences between groups or sessions at p < 0.05 as evaluated by a t-test on session-averaged data are indicated by an asterisk (*), n.s. indicates a non-significant result.
Mentions: First we tested rats in the MMW (Figure 1). There were four acquisition sessions in the hidden platform version of the MWM with the platform located in the NE and pseudorandom starting positions. In these sessions, Samaritan rats needed longer paths to locate the platform, indicating that they were impaired. The mixed effects ANOVA (groups × sessions × swims) revealed a significant main effect of group (F(1,13) = 12.62; p < 0.05), sessions (F(3,39) = 4.76; p < 0.05), swims (F(5,65) = 10.57; p < 0.05) and interaction between groups and session (F(3,39) = 4.41; p < 0.05). No other interactions, including a triple interaction between swims, sessions and groups, were detected. The total distance to reach the platform in a particular session is illustrated in Figure 1A-left; though individual swims are not depicted, the total distance decreased in both groups for subsequent swims each day.

Bottom Line: Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function.Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately.Our results show that Samaritan rats(™) exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of SciencesPrague, Czech Republic; National Institute of Mental HealthKlecany, Czech Republic.

ABSTRACT
Alzheimer's disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta42 (Abeta42) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats(™) exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages.

No MeSH data available.


Related in: MedlinePlus