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Evaluation of Nicotinic Acetylcholine Receptors in Learning and Memory Using Mouse Model of Alzheimer’S Disease

Thesis Info

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Author

Farhat, Mehpara

Program

PhD

Institute

National University of Sciences & Technology

City

Islamabad

Province

Islamabad

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Natural Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/8361/1/Syeda_Mehpara_Farhat_Viro_%26_Immuno_2017_HSR_NUST_14.12.2017.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726130180

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Background: Aluminum (Al) is known to be associated with etiology of different neurodegenerative disorders especially of Alzheimer’s disease (AD) and is known to produce AD like symptoms. It is widely reported that Al affects muscarinic acetylcholine receptors but limited data is available for its effects on nicotinic acetylcholine receptors (nAChRs). The aim of this study was to determine that how Al affects hippocampus, amygdala and cortex dependent learning and memory functions and expression of nAChRs and choline acetyltransferase (ChAT) genes. Effect of Al on cholinergic biomarkers i.e. free choline and acetylcholine (Ach) level were also investigated. Moreover acute effects of Al on nAChRs-mediated modulation of persistent gamma oscillations in hippocampus was also studied. Methods: In order to develop the AD mouse model, AlCl3.6H2O (250 mg/kg) was administered to mice in drinking water 42 days. After completion of Al treatment the learning and memory deficits were assessed via different behavior tests. nAChRs gene expression was determined via RT-PCR in cortex, hippocampus and amygdala. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to measure Al accumulation in brain. To determine how Al affects gamma oscillations, field potential recordings were performed in CA3 area of acute hippocampal slices. Results: The results of this study demonstrate that oral Al ingestion caused high accumulation of Al in brain leading to neuropathological changes that suppressed expression of nAChR genes and caused neurodegeneration. Longer in-vitro Al exposure caused permanent changes in hippocampal oscillogenic circuitry and changed its sensitivity to nAChR-modulation, leading to deficits in memory and learning in AD mouse model. Moreover in spite of normal free choline availability Abstract xix Ach synthesis was reduced as a result of oral Al exposure. The reduced Ach synthesis is caused by impaired recycling of Ach due to lower expression of ChAT gene. The reduced Ach level causes deficits in cholinergic neurotransmission which leads to memory and cognitive deficits. Moreover, hippocampus is the most affected brain part after Al intoxication. This study suggests that interference with cholinergic neurotransmission can be the underlying mechanism through which Al causes memory and learning deficits and contributes to neuropathological changes leading to AD.
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5۔ تحفظ مال

5۔ تحفظ مال
مقاصد شریعت میں ایک اہم مقصد ما ل کی حفا ظت ہے۔ بنیادی ضرریات کی تکمیل کے لیے روپے پیسے اور مال کا ہونا ضروری ہے اس کے بغیر زندگی گزارنا محال ہے اور اس کا حصول بعض اوقات انسان کو موت اور کفر تک پہنچا دیتا ہے اور باعث فتنہ ہے۔ اسلام انسان کے مال کے تحفظ کے لئے اقدامات کرتا ہے اور ناجائز ذرائع سے مال کا حاصل کرنا حرام قرار دیتا ہے، جیسا کہ ارشاد باری تعالیٰ ہے:
﴿وَلَا تَأْكُلُوا أَمْوَالَكُمْ بَيْنَكُمْ بِالْبَاطِلِ ۔ ﴾253
"اور تم ایک دوسرے کا مال ناحق طریقے سے نہ کھاؤ۔ "
اس آیت کی رو سے اللہ تعالیٰ نے ہر اس طریقے سے مال کمانا حرام قرار دیا ہے جو غیر قانونی ہو اور جس کے ذریعے سے دوسرے کے مال کو ناجائز طریقے سے لینے کی کوشش کی جاتی ہو یہی وجہ ہے کہ اسلام نے مال کے مالک کو یہ ہدایت کی ہے کہ وہ حلال ذریعہ سے کمائے گئے اپنے مال کی حفا ظت کرے ۔
انسان کو دین ، اولاد ، جان اور مال بہت پیارا ہوتا ہے ان کے لیے وہ سر دھڑ کی بازی تک لگا دیتا ہے۔ اسلام نے اپنے مال کی حفاظت کرتے ہوئے مرنے والے فرد کو شہید کہا ہے ۔ عبداللہ بن عمر سے مروی ہے کہ رسول اللہ ﷺ نے ارشاد فرمایا
"مَن قُتِلَ دونَ مالِهِ؛ فهو شَهيدٌ "254
"جو اپنے مال کی حفاظت کرتے ہوئے قتل ہو جائے ، پس وہ شہید ہے۔ "
مالک کو ہدایت کی جا رہی ہے کہ مال کی حفاظت کے سلسلے میں ظاہری اسباب کو اختیار کرے، پھر اللہ تعالیٰ پر توکل کرے اور مال کو دوسروں کے رحم وکرم پر نہ چھوڑے ، جیسا کہ رسول اللہ ﷺ نے ارشاد فرمایا
"اعْقِلْهَا وَتَوَكَلْ ۔"255

امام جلال الدین سیوطی کی الخصائص الکبری کا اسلوب ومنہج

Imām Jalāl-ud-Dīn Suyūtī (d.911 A.H.)– a great personality of Islām, devoted his entire life for the services of Islām. He authored a number of books on multiple disciplines of Islām. One worth-mentioning contribution of Imām Suyūtī is his book ‘Al Khaṣāiṣ al Kubra’. A number of Arab researchers have compiled analytical research works on specific topics and certain chapters of the book. However, a collective analysis on the pattern and methodology of the book is not present so far. Therefore, this article deals with a holistic and collective discussion on the approach and patterns of the book for the first time in Urdu language. The article enlightens its readers with a comprehensive introduction of the book in the beginning. However, lately, it thoroughly reviews and analyzes the style and method of Imām Jalāl-ud-Dīn Suyūtī. Moreover, the article also contains details of the significance and genuine qualities of the book along with its distinctive features. The study concludes that the worthwhile work of Imām Jalāl-ud-Dīn Suyutī in this particular field deserves to be acknowledged genuinely.

Seroprevalence of Toxoplasmosis, Hematological and Serum Biochemical Profile in Sheep in Multan and Khanewal Districts, Punjab Pakistan .

The present study was conducted to determine the seroprevalence of toxoplasmosis, hematological and serum biochemical changes in sheep naturally infected with Toxoplasma gondii and compared between T. gondii positive and negative sheep in Multan and Khanewal districts, Punjab (Pakistan).Blood samples were collected from 500 sheep and T. gondii antibodies were tested by latex agglutination test (LAT) and Enzyme Linked Immunosorbent Assay (ELISA).Information related to hosts and herds were recorded on questionnaire basis such as gender, age of animals, aborted or non-aborted sheep, cats association with herd, method of disposing aborted fetuses and herd size.The overall prevalence of toxoplasmosis in sheep was 33.6% by latex agglutination test (LAT) and 27.4% by ELISA (P-value = 0.033, OR = 1.341, 95 % CI = 1.023, 1.757).The area wise prevalence of toxoplasmosis was 34.02% and 33. 01 % by LAT (P-value = 0.813, OR = 1.031, 95 % CI = 0.802, 1.324) in Multan and Khanewal and 28.12 % and 26.41 % by ELISA (P-value = 0.672, OR = 1.065, 95 % CI = 0.796, 1.424) in Multan and Khanewal respectively.Difference was statistically non-significant (P>0.05).The seroprevalence of toxoplasmosis was compared between aborted and non-aborted sheep and according to these results infection rate was 51.66% and 31.10% in aborted and non-aborted sheep by LAT (P-value = 0.002, OR = 1.661, 95 % CI = 1.248, 2.211) and 41.66 % and 26.22% in aborted and non-aborted sheep by ELISA (P-value = 0.013, OR = 1.589, 95 % CI = 1.128, 2.238) respectively.Difference was statistically significant (P<0.05) by both techniques.The relationship between sex of sheep and toxoplasmosis showed that infection was 31.37% and 33.85 % by LAT (P-value = 0.722, OR = 0.927, 95 % CI = 0.605, 1.419) in males and females respectively.Similarly prevalence was 19.6 % and 28.28% by ELISA (P-value = 0.188, OR = 0.693, 95 % CI = 0.390, 1.232) in males and females respectively.The prevalence was higher in females than males and difference was statistically non-significant (P>0.05) by both techniques.The prevalence of T. gondii was compared between different age groups and according to these findings infection rate was higher in age group 60-73 months (64.5% and 38.7%) and lowest in age group 4-17 months (26.4% and 22.4%) by LAT (P-value = 0.001) and ELISA (P-value = 0.404).Difference was statistically significant (P<0.05) by LAT and non-significant (P>0.05) by ELISA.Risk factors associated with prevalence of toxoplasmosis in sheep were also studied and according to these results a large flock size, presence of cats, and the aborted fetuses openly left on ground were all statistically significant (P≤0.05) risk factors that were positively associated with prevalence of toxoplasmosis in sheep flocks.Hematological and serum biochemical parameters were studied between T. gondii positive and negative sheep andaccording to these results mean values of haemoglobin, glucose, cholesterol, AST, ALT and LDH were 9.5 ± 2.6 g/dL, 50.6 ± 11.3 mg/dL, 211.6 ± 79.6 mg/dL, 216.4 ± 144.4 U/L, 79.0 ± 64.1 U/L, 613.9 ± 297.2 U/L in T. gondii positive sheep by LAT and 9.9 ± 3.1 g/dL, 52.3 ± 11.3 mg/dL, 198.5 ± 73.6 mg/dL, 209.44 ± 629.3 U/L, 98.7 ± 228.7 U/L, 578.3 ± 292.9 U/L in T. gondii negative sheep respectively.Similarly mean values of haemoglobin, glucose, cholesterol, AST, ALT and LDH were 9.5 ± 2.5 g/dL, 50.6 ± 11.3 mg/dL, 214.6 ± 79.9 mg/dL, 217.3 ± 140.7 U/L, 77.8 ± 66.4 U/L, 606.8± 291.5 U/L in T. gondii positive sheep by ELISA and 9.9 ± 3.1 g/dL, 52.3 ± 11.2 mg/dL, 198.4± 73.8 mg/dL, 209.6 ± 605.1 U/L, 97.6 ± 219.8 U/L, 583.8 ± 295.7 U/L in T. gondii negative sheep respectively.Hemoglobin, glucose and ALT concentration was lower in T. gondii positive sheep as compared to T. gondii negative sheep.Cholesterol, AST and LDH concentration was higher in T. gondii positive sheep than T. gondii negative sheep.Haemoglobin, Glucose, AST, ALT and LDH values varied statistically non-significantly (P>0.05) between T. gondii positive and negative sheep whereas cholesterol level varied statistically significantly (P<0.05) between T. gondii positive and negative sheep. In conclusion, cholesterol level was found higher in sheep infected with toxoplasmosis which may lead to certain complications including coronary artery diseases, myocardial infarction, atherosclerosis, hypertension, hemorrhage and vascular thrombosis in infected sheep.T. gondii is a blood parasite which can cause abortion, fetal death, stillbirth, neonatal death in sheep which can lead toward economic losses such as reduction in fur, wool, meat, milk and other dairy products etc. The results indicated the overall high rates of seroprevalence of T. gondii in sheep that warranted the threat to public health especially farmers and abattoir workers via zoonotic transmission of toxoplasmosis.Keeping in view, the medical and veterinary importance of T. gondii it is recommended that human population (especially farmers and abattoir workers), other livestock species and stray cats present in study area must also be screened for the Toxoplasma infection in the public interest.