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Melatonin Supplementation Alleviates Impaired Spatial Memory by Influencing Aβ 1-42 Metabolism via γ-Secretase in the icvAβ 1-42 Rat Model with Pinealectomy.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Sep 24; Vol. 25 (19). Date of Electronic Publication: 2024 Sep 24. - Publication Year :
- 2024
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Abstract
- 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 <subscript>1-42</subscript> 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 <subscript>1-42</subscript> oligomers (icvAβ <subscript>1-42</subscript> ) combined with melatonin deficiency via pinealectomy (pin). We validated this model by assessing spatial memory using the radial arm maze test and measuring Aβ <subscript>1-42</subscript> and γ-secretase levels in the frontal cortex and hippocampus with ELISA. The icvAβ <subscript>1-42</subscript> + pin model experienced impaired spatial memory and increased Aβ <subscript>1-42</subscript> and γ-secretase levels in the frontal cortex and hippocampus, effects not seen with either icvAβ <subscript>1-42</subscript> or the pin alone. Chronic melatonin treatment reversed memory deficits and reduced Aβ <subscript>1-42</subscript> and γ-secretase levels in both structures. Our findings suggest that our icvAβ <subscript>1-42</subscript> + pin model is extremely valuable for future AD research.
- Subjects :
- Animals
Rats
Male
Memory Disorders drug therapy
Memory Disorders metabolism
Memory Disorders etiology
Maze Learning drug effects
Melatonin pharmacology
Melatonin metabolism
Amyloid beta-Peptides metabolism
Amyloid Precursor Protein Secretases metabolism
Spatial Memory drug effects
Disease Models, Animal
Peptide Fragments metabolism
Alzheimer Disease metabolism
Alzheimer Disease drug therapy
Pinealectomy
Hippocampus metabolism
Hippocampus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39408624
- Full Text :
- https://doi.org/10.3390/ijms251910294