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Selective biomarkers as predictive tools in investigating the efficacy of liposomal Coenzyme- Q10 in the autistic rat model / by Doaa Mousa Mostafa Elhefnawei ; Supervisors Prof. Dr. Mohamed Ali El-Desouky , Prof. Dr. Mohamed Ahmed Badawy , Prof. Dr. Ahlam Hosny Mahmoud , Prof. Dr. Mai Osman Mohamed.

By: Contributor(s): Material type: TextTextLanguage: English Summary language: English, Arabic Producer: 2023Description: 121 pages : illustrations ; 25 cm. + CDContent type:
  • text
Media type:
  • Unmediated
Carrier type:
  • volume
Other title:
  • / Coenzyme-Q10 انتقاء المؤشرات الحيوية كدلالات تنبؤية لفاعلية ليبوزومات فى نموذج الجرذان التوحدى [Added title page title]
Subject(s): DDC classification:
  • 660.6
Available additional physical forms:
  • Issues also as CD.
Dissertation note: Thesis (Ph.D)-Cairo University, 2023. Summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition with genetic and environmental origin marked by disturbance in social interaction and repetitive behaviors. Propionic acid (PPA) is considered as a successful autism animal model. Treatment of neurodegenerative diseases has tremendous therapeutic potential for Coenzyme-Q10 (CoQ10). Nevertheless, its low water solubility limited its therapeutic applications. Liposomal drug delivery possesses the benefits of biocompatibility, targeting organs and avoiding macrophages. The present study objective is assessing the effectiveness of CoQ10 and liposomal Coenzyme- Q10 (LCoQ10) on PPA-mediated autistic rat model. Liposomes are efficient for delivering CoQ10 across the brain-blood barrier (BBB) and reaching the target organ. PPA (500 mg/kg Bw in phosphate buffer saline) was given daily for five days to induce autism, then receiving therapy with CoQ10 (10 mg/kg BW) and LCoQ10 (2 mg/kg BW) for 30 days. The model was monitored for autism symptoms at various time intervals of (one, two and four weeks). Behavioral tests (Y- Maze and Open field), Gamma-amino butyric acid (GABA), Acetylcholine (ACh), Acetylcholinesterase (AChE) activity and antioxidant analysis were all accomplished in control, PPA and treated groups. Glial fibrillary acidic protein (GFAP), Calcium Voltage-Gated Channel Subunit Alpha 1 C (CACNA1C), Brain-Derived Neurotrophic Factor (BDNF), cAMP Response Element-Binding Protein (CREB) and Methyl-CpG-binding Protein 2 (MeCP2) gene expression were also performed. COMET assay and histological examination were also confirmatory. Superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC) revealed considerable increases via CoQ10 and LCoQ10 treatment in contrast to MDA. Moreover, they significantly down regulated GABA, AChE and the gene expression of GFAP, CACNA1C and BDNF. Furthermore, they up regulated ACh, the gene expression of CREB and MeCP2. They also improved DNA damage and PPA histopathological abnormalities and LCoQ10 showed even better results. In conclusion, targeting organs and extending retention time via LCoQ10 treatment may be a potential technique for limiting aberrant behaviors in PPA- induced autism rat model. Summary: اضطراب طيف التوحد (ASD) هو واحد من أكثر الاضطرابات المربكة ل التي لم يتم تحديد سبب محدد فحسب ، بل لم يتم أيضا تحديد أي علاج نهائي لها تم العثور عليها حتى الآن. التوحد هو اضطراب يتم ملاحظته عادة على الطفل في سن مبكرة ، تؤثر على الجوانب التنموية المختلفة. تطورها غير طبيعي. إنه يظهر خللا في تفاعله الاجتماعي ، يتميز بتكرار بعض الأنماط السلوكية والتحديات في التواصل اللفظي وغير اللفظي مع الاخرين. على مدى العقود القليلة الماضية ، أظهر انتشاره ارتفاعا كبيرا. و الملاحظة التي شجعت العديد من الباحثين في جميع أنحاء العالم على محاولة استكشاف جميع جوانبه من المسببات إلى التشخيص والتدخل. ASD هو نوع من اضطراب النمو العصبي الذي يتميز بضعف التواصل الاجتماعي و التفاعلات المتكررة ، وكذلك المصالح المحدودة. يرتبط حمض البروبيونيك (PPA) بالسلوكية والعصبية المرضية و تشوهات كيميائية حيوية لوحظت في ASD.
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Thesis Thesis قاعة الرسائل الجامعية - الدور الاول المكتبة المركزبة الجديدة - جامعة القاهرة Cai01.12.02.Ph.D.2023.Do.E (Browse shelf(Opens below)) Not for loan 01010110088966000

Thesis (Ph.D)-Cairo University, 2023.

Bibliography: pages 93-121.

Autism spectrum disorder (ASD) is a neurodevelopmental condition with genetic and
environmental origin marked by disturbance in social interaction and repetitive behaviors.
Propionic acid (PPA) is considered as a successful autism animal model. Treatment of
neurodegenerative diseases has tremendous therapeutic potential for Coenzyme-Q10 (CoQ10).
Nevertheless, its low water solubility limited its therapeutic applications. Liposomal drug
delivery possesses the benefits of biocompatibility, targeting organs and avoiding macrophages.
The present study objective is assessing the effectiveness of CoQ10 and liposomal Coenzyme-
Q10 (LCoQ10) on PPA-mediated autistic rat model. Liposomes are efficient for delivering
CoQ10 across the brain-blood barrier (BBB) and reaching the target organ. PPA (500 mg/kg Bw
in phosphate buffer saline) was given daily for five days to induce autism, then receiving therapy
with CoQ10 (10 mg/kg BW) and LCoQ10 (2 mg/kg BW) for 30 days. The model was monitored
for autism symptoms at various time intervals of (one, two and four weeks). Behavioral tests (Y-
Maze and Open field), Gamma-amino butyric acid (GABA), Acetylcholine (ACh),
Acetylcholinesterase (AChE) activity and antioxidant analysis were all accomplished in control,
PPA and treated groups. Glial fibrillary acidic protein (GFAP), Calcium Voltage-Gated Channel
Subunit Alpha 1 C (CACNA1C), Brain-Derived Neurotrophic Factor (BDNF), cAMP Response
Element-Binding Protein (CREB) and Methyl-CpG-binding Protein 2 (MeCP2) gene expression
were also performed. COMET assay and histological examination were also confirmatory.
Superoxide dismutase (SOD), reduced glutathione (GSH), and total antioxidant capacity (TAC)
revealed considerable increases via CoQ10 and LCoQ10 treatment in contrast to MDA.
Moreover, they significantly down regulated GABA, AChE and the gene expression of GFAP,
CACNA1C and BDNF. Furthermore, they up regulated ACh, the gene expression of CREB and
MeCP2. They also improved DNA damage and PPA histopathological abnormalities and
LCoQ10 showed even better results. In conclusion, targeting organs and extending retention time
via LCoQ10 treatment may be a potential technique for limiting aberrant behaviors in PPA-
induced autism rat model.

اضطراب طيف التوحد (ASD) هو واحد من أكثر الاضطرابات المربكة ل
التي لم يتم تحديد سبب محدد فحسب ، بل لم يتم أيضا تحديد أي علاج نهائي لها
تم العثور عليها حتى الآن. التوحد هو اضطراب يتم ملاحظته عادة على الطفل في
سن مبكرة ، تؤثر على الجوانب التنموية المختلفة. تطورها غير طبيعي. إنه
يظهر خللا في تفاعله الاجتماعي ، يتميز بتكرار بعض
الأنماط السلوكية والتحديات في التواصل اللفظي وغير اللفظي مع
الاخرين. على مدى العقود القليلة الماضية ، أظهر انتشاره ارتفاعا كبيرا. و
الملاحظة التي شجعت العديد من الباحثين في جميع أنحاء العالم على محاولة استكشاف جميع
جوانبه من المسببات إلى التشخيص والتدخل. ASD هو نوع من
اضطراب النمو العصبي الذي يتميز بضعف التواصل الاجتماعي و
التفاعلات المتكررة ، وكذلك المصالح المحدودة.
يرتبط حمض البروبيونيك (PPA) بالسلوكية والعصبية المرضية و
تشوهات كيميائية حيوية لوحظت في ASD.

Issues also as CD.

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