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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 of western blotting. Representative images of samples from the L hemisphere were used (all data are presented in Table 2).
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Figure 3: Results of western blotting. Representative images of samples from the L hemisphere were used (all data are presented in Table 2).

Mentions: Table 2 shows the expression levels of NR1/NR2A/NR2B in the R and L frontal cortices. For representative image of western blot results, see Figure 3. In the sham-operated Long Evans controls, no marked asymmetries were found in NR1 (index of laterality = +0.005) or in NR2A subunit (index of laterality = −0.010). On the other hand, mild L/R dominance was observed in the NR2B subunit (index of laterality = +0.056, there was an increase to 112% in the L compared to the R cortex, and the results of ANOVA with repeated measures for laterality was significant, p < 0.001). In Samaritan rats compared to the controls, results of ANOVA with repeated measures and one-way ANOVA only showed a significant change in the NR2A subunit (an increase to 102% in the L side of Samaritan rats). Although the results of the global test also suggested possible effects of laterality in the NR1 and NR2B subunits (with a drop to 98% of NR1 and an increase to 104% of NR2B in Samaritan rats, in both cases in the R side), results of one-way ANOVA did not support this.


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 of western blotting. Representative images of samples from the L hemisphere were used (all data are presented in Table 2).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Results of western blotting. Representative images of samples from the L hemisphere were used (all data are presented in Table 2).
Mentions: Table 2 shows the expression levels of NR1/NR2A/NR2B in the R and L frontal cortices. For representative image of western blot results, see Figure 3. In the sham-operated Long Evans controls, no marked asymmetries were found in NR1 (index of laterality = +0.005) or in NR2A subunit (index of laterality = −0.010). On the other hand, mild L/R dominance was observed in the NR2B subunit (index of laterality = +0.056, there was an increase to 112% in the L compared to the R cortex, and the results of ANOVA with repeated measures for laterality was significant, p < 0.001). In Samaritan rats compared to the controls, results of ANOVA with repeated measures and one-way ANOVA only showed a significant change in the NR2A subunit (an increase to 102% in the L side of Samaritan rats). Although the results of the global test also suggested possible effects of laterality in the NR1 and NR2B subunits (with a drop to 98% of NR1 and an increase to 104% of NR2B in Samaritan rats, in both cases in the R side), results of one-way ANOVA did not support this.

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