الفهرس 
ACKNOWLEDGEMENTOnly 14 pages are availabe for public view
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Abstract
PD is a chronically progressive, age related, neurodegenerative movement disorder affecting about 1% of the worldwide population over the age of 60. It is marked by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Genetic predisposition accounts for early onset PD while sporadic cases are more common and usually occur later in life. Oxidative stress and mitochondrial dysfunction are the main neurodegenerative mechanisms in both genetic and sporadic PD. Till now there is no definite cure for PD, available medications provide only symptomatic treatment of motor symptoms and also cause many side effects. In this experimental study, we used nicotine (a pyridine alkaloids) which is a potent para sympathomimetic stimulant acting as receptor agonist at most nicotinic acetylcholine receptors. Forty adult healthy male albino rats were used in this study and divided randomly into 3 groups: -group I: (Normal-control, n=10): This group received subcutanous injection of normal saline (1 ml/kg body weight) once daily for for 11 days. -group II: (Parkinson’s-diseased group, n=20): Parkinsonism was induced in rats by subcutaneous injection of rotenone at a dose of 1.5 mg/kg in 6 doses every other day for 11 days, dissolved in equal amounts of (DMSO +PEG-300) in volume of 5 ml/kg to induce experimental parkinsonism. This group is subdivided equally into 2 subgroups: -group IIA (Parkinson control group, n=10): Rats were kept without further treatment after induction of Parkinson’s disease. -group IIB: (Parkinson treated group, n=10): This group received nicotine at a dose of 1.5 mg/kg body weight dissolved in normal saline 5ml/kg, injected subcutaneously once per day for 11 days. -group III: (Nicotine control group, n=10): This group was injected subcutaneously with nicotine dissolved in normal saline at a dose of 1.5 mg/kg body weight once daily for 11 days. At the end of the experiment, bodyweight was estimated, physiological tests were done for assessment of the locomotor activity, and blood samples were taken for assessment of total antioxidant capacity (TAC) and serum malondialdehyde (MDA) levels. Striatal dopamine levels were measured. Specimens of the midbrain were processed for the histological, morphometric, and immunohistochemical study of the SNc Rotenone treatment induced parkinsonian like symptoms and deterioration in the rat motor performance as noticed by physiological tests, with a marked increase in oxidative stress markers. Apoptotic neuronal loss in SNc was detected by immunohistochemistry, histological, and morphometric analysis. Immunoreactivity revealed a marked decrease in the number of TH positive neurons and increase in the number of Caspase 3 positive neurons. Morhometric analysis revealed an increase in the number of dark cells per field. Ultra-structurally neurons revealed marked reduction in Nissl granules, membrane –bound α synuclein inclusions, fragmented Golgi along with disorganized microtubules, and enlarged vesicular mitochondria in neuronal processes. Glial cell alteration included mild upregulation of glial fibrillary acidic protein (GFAP) in astrocytes. Ultra-structurally astrocytes exhibited vesicular mitochondria and / or disrupted outer membrane, fragmented Golgi, and α-synuclein protein might be found inside the astrocytic process. Oligodendrocytes characteristically revealed membrane-bound inclusions. Dark microglia with electron dense cytoplasm and hyperchromatic nuclei were evident. Vascular vulnerability was manifested by endothelial disruption and degeneration indicating blood-brain barrier dysfunction. Nicotine treatment of the rotenone induced rat model of PD produced improvement in motor performance, and striatal dopamine levels, a significant reduction in the serum levels of MDA and a significant rise in the TAC serum levels. Immunohistochemistry and morphometry revealed an increase in the TH positive neurons, a decrease in the caspase 3 positive neurons with a decrease in the number of dark cells per field. Improvement in the ultrastructural neuronal morphology has also been depicted. Nicotine treatment in control rats induced neuronal activation followed by exhaustion. Immunoreactivity revealed decreased TH-positive neurons, mild positive reactivity to caspase 3, α-synuclein, and GFAP antibodies. In ultrastructure, some neurons showed a marked increase in Nissl bodies, others exhibited fragmented Golgi apparatus and / or disorganized microtubules of the dendritic processes. Nicotine treatment negatively affected the integrity of the blood brain barrier with remarkable endothelial and pericytic apoptotic changes.