الفهرس 
ReviewOnly 14 pages are availabe for public view
 |  | from | 284 |  |  |
| | | from | 284 | | |
Abstract
Summary
Alzheimer’s disease is a type of brain disease. It is also a degenerative disease, meaning that it becomes worse with time. Alzheimer’s disease is thought to begin 20 years or more before symptoms arise, with changes in the brain that are unnoticeable to the person affected. Only after years of brain changes do individuals experience noticeable symptoms such as memory loss and language problems. As the disease progresses, neurons in other parts of the brain are damaged or destroyed. Eventually, nerve cells in parts of the brain that enable a person to carry out basic bodily functions, such as walking and swallowing, are affected. Individuals become bed-bound and require around-the-clock care. Alzheimer’s disease is ultimately fatal.
This study included 70 male Wistar rats divided into four groups; normal control, Alzheimer Disease (AlCl₃), therapeutic I (5 mg kg b.w. Ivermectin plus AlCl₃) and Therapeutic II (10 mg kg b.w Ivermectin plus AlCl₃) for 4 consecutive weeks. At the end of the treatment period, brain was excised and divided three parts part was fixed in 10 % formalin for histopathological examination, part for the biochemical parameter study while the rest was used for RNA isolation. Physical behavioral studies were performed to confirm the incidence of AD and the efficiency of Ivermectin.
The results obtained are summarized as follows:
1-Physical Behavior Studies
Injection of rats with aluminum chloride induced AD’s characteristics (memory insufficient and behavioral impairment) by raising the time spent (6.5 min) to complete the session and the number of errors (4.44 errors), compared to the normal control group (2.84 min with 1.39 errors). On the other hand, treatment of AD-bearing rats with Ivermectin reduced the time spent at therapeutic І and therapeutic ІІ groups (4.67 and 3.61 min, respectively) to complete the session and the number of errors (2.43 and 1.44 errors, respectively) per session, compared to AD-bearing rats.
2- Biochemical parameters
2.1-Oxidative stress markers
Administration of aluminum chloride significantly elevated the contents of AOPP and protein carbonyl (176.73% and 114.61%, respectively) in brain at p > 0.0001, in association with a significant reduction in the antioxidant enzymes activity (SOD and GPx) by 87.82 and 79.44%, respectively, at p > 0.0001, compared to the normal control group. On the other hand, treatment of AD rats with Ivermectin (5mg/kg b.w) improved AOPP contents as well as SOD and GPx activities in brain, compared to AD group, but were still differ from the normal control levels (93.03, -35.36, and -16.2%, respectively, at p >.0001). While the protein carbonyl content in brain returned to the normal (11.52 at p > 0.0001). Post treatment of AD-bearing rats with 10 mg/ kg b.w. Ivermectin returned the balance between oxidants and antioxidants to the normal levels, except for brain SOD activity which was improved but was still lower than the normal activity by 29.61 % (p > 0.0001).
2.2- Alzheimer Markers of AD
2.2.1-Brain amyloid-β and tau proteins
Administration of AlCl₃ elevated the content of amyloid β and Tau in brain tissue (451.45 and 258.49 respectively, at p > 0.0001), compared to the normal control group. Injection of both doses of Ivermectin (5 and 10 mg/kg b.w.) in AD rats significantly reduced amyloid β and Tau, compared to AD group, but were still significantly higher than the normal control group (171.01 and 98.11 % at p > 0.0001) and (167.44 and 103.77 % at p > 0.0001), respectively.
2.2.1- Brain metals
Administration of AlCl₃ increased the content of calcium and aluminum in brain tissue by 926, and 1850 %, respectively at p > 0.0001, compared to the normal control group. Injection of Ivermectin (5 and 10 mg/kg b.w.) in rats normalized the brain caᶧ² and Al contents by (-10 and 50 % at p > 0.0001) and (-4 and 50 % at p > 0.0001), respectively.
3- Histopathological investigations
Administration of AlCl3 to rats induced AD which is characterized histologically by hippocampus with markedly degenerated neuronal cells with a deposition of eosinophilic amyloid-like material. In addition, eosinophilic plaque surrounding thick-walled blood vessels with atrophied nerve cells and scattered degenerated neuronal cells were seen in the white matter of brain. Also, white matter of brain in rats-bearing AD had a marked spongiosis and microcystification with markedly degenerated neuronal cells. Treatment of AlCl3-induced Alzheimer’s disease with Ivermectin (therapeutic І) showed a cerebral cortex with normal neuronal cells, blood vessel, average astrocytes, and average fibrils. In Ivermectin (therapeutic ІІ) group, the hippocampus had average neurons. Furthermore, the cerebral cortex had average pyramidal cells, average stellate cells, and average fusiform cells.
4- Molecular studies
Injection with AlCl₃ induced a significant increase in the expression levels of amyloid β, glycine receptor α₂ and α₃ genes in brain (p> 0.0001). On the other hand, treatment of AD rats with both therapeutic doses of Ivermectin (5 and 10 mg/kg b.w.) caused a significant decrease in the expression level of amyloid β, glycine receptor α₂ and α₃ genes compared to AD group (p > 0.0001) towards the normal expression levels.