الفهرس 
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Abstract
Alzheimer’s disease is a chronic and progressive neurodegenerative disease that accounts for dementia and mental deterioration in the elderly. AD usually starts slowly and worsens over time.AD characterized by disruption regarding memory, reason, punishment, and multiple cognitive deficiencies including thinking process, learning ability, orientation, calculation, and language that interferes with a person’s everyday lifestyles or activities.
The available treatments of AD are not disease-modifying drugs, decelerate the progression of the disease, provide symptomatic relief but fail to achieve a definite cure. Astaxanthin (ATX) is a dark red carotenoid. It is considered as a second generation antioxidant with strong antioxidant, anti-inflammatory, neuroprotective and anti-apoptotic effects. ATX has as high as 10 times more antioxidant power than other carotenoids; with it being 500-fold higher than that of vitamin E as a singlet oxygen (O2•) quencher and 100 times more than α-tocopherol with respect to the protective effects against lipid peroxidation. ATX provides protection to protect immune system defenses from free radical damages.Crossing the blood brain barrier (BBB), it allows free entry to the central nervous system.
The aim of the present study was to explore the possible therapeutic effect of astaxanthin (ATX) on Alzheimer’s disease-like rat model (AD-like) at different levels; behavioral, amyloidogenic pathway, neurotransmitters and catabolizing enzymes, and gene expression of two genes responsible for controlling mitochondrial biogenesis (PGC-1α and Tfam).
The study was conducted on 50 male albino rats (3 months old and weights ranging from 100-150gm).Alzheimer’s disease-like model was induced using hydrated aluminum chloride (AICI3.6H2O) solution that was given orally at a dose of 75 mg/kg body weight (b.wt)daily for 6 weeks. The Morris water maze (MWM) test was performed at the end of the6 weeks to assess the spatial memory and prove the cognitive impairments in the rats. The animals were divided into two groups; group I (Control group): consisted of 10 healthy male rats that was orally treated with dimethyl sulfoxide (DMSO). group II (AD group): consisted of 40 Alzheimer-like rats that wassubdivided into four subgroups: group IIA: consisted of 10 untreated Alzheimer-like rats that was orally treated with DMSO. GroupsIIB, IIC and IIDconsisted of 10 Alzheimer-like rats each that were orally treated with different doses of astaxanthin dissolved in DMSO; 5, 10 and 15 mg/kg b.wt /day respectively for six weeks.
After the last day of treatment, Animals were subjected to the behavioral test (MWM) then sacrificed by cervical dislocation and the brain was dissected. The cortex and hippocampus were excised from the hemisphere for the determination of (Aβ1-42), Acetylcholine,Acetylcholinesterase activity, Serotonin, Monoamine oxidase activity and total RNA extraction for quantitative real time polymerase chain reaction (qPCR)for the determination ofPeroxisome proliferator‐activated receptor‐gamma coactivator‐1alphaand mitochondrial transcription factor A gene expression.
The AD-like rats had significantly lower contents of the acetylcholine (ACh) and serotonin in brain cortex and hippocampus. While the activities of acetylcholinesterase (AChE) and monoamine oxidase (MAO) showed higher activities especially in the cortex. The same rats marked increase in Aβ1-42 content in the cortex and hippocampus witha significant down-regulation in the expression of the genes involved in the regulation of mitochondrial biogenesis; peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (Tfam).
Astaxanthin treatment significantly and dose-dependently amended the performance of AD-like rats treated with different doses of ATX during Morris Water Maze andcaused a significant increase in the cortical and hippocampus contents of ACh and serotonin. These increases were associated with a significant decline in the activities of AChE, MAOand Aβ1-42 content. Also, ATX showeda significant up-regulation and nearly complete normalization of PGC-1α and Tfam expression in the cortex and hippocampus.
from the above-mentioned results, it can be concluded that:
• Astaxanthin has powerful dose-dependent therapeutic effects in the AD-like rat model.
• The ATX targets multiple pathways that play key roles in the development and progression of AD including; impaired cholinergic and serotonergic neurotransmissions, amyloidogenic pathway, and mitochondrial dysfunction.
• ATX has multiple actions to target these pathways including, inhibition of AChE and MAO, enhancing PGC-1α and Tfam expression and boosting mitochondrial biogenesis, and improving the cognitive and behavioral performance of the AD-like rats.
• All of these effects together with the safety and no adverse effects of ATX make it a promising therapeutic agent for Alzheimer’s disease management.
• Future studies are recommended to explore the protective and therapeutic action of ATX in AD patients.