| Autor: |
Georgieva I; Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria., Tchekalarova J; Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria., Nenchovska Z; Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria., Kortenska L; Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 23, 1113 Sofia, Bulgaria., Tzoneva R; Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 21, 1113 Sofia, Bulgaria. |
| Abstrakt: |
In the search for Alzheimer's disease (AD) therapies, most animal models focus on familial AD, which accounts for a small fraction of cases. The majority of AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in AD progression, dysfunction in γ-secretase causes the formation of insoluble Aβ 1-42 peptides, which aggregate into senile plaques, triggering neurodegeneration, cognitive decline, and circadian rhythm disturbances. To better model sporadic AD, we used a new AD rat model induced by intracerebroventricular administration of Aβ 1-42 oligomers (icvAβ 1-42 ) combined with melatonin deficiency via pinealectomy (pin). We validated this model by assessing spatial memory using the radial arm maze test and measuring Aβ 1-42 and γ-secretase levels in the frontal cortex and hippocampus with ELISA. The icvAβ 1-42 + pin model experienced impaired spatial memory and increased Aβ 1-42 and γ-secretase levels in the frontal cortex and hippocampus, effects not seen with either icvAβ 1-42 or the pin alone. Chronic melatonin treatment reversed memory deficits and reduced Aβ 1-42 and γ-secretase levels in both structures. Our findings suggest that our icvAβ 1-42 + pin model is extremely valuable for future AD research. |
