Exploratory mechanistic study of a novel antipsychotic drug in an experimental model of schizophrenia in rats / (رقم التسجيلة. 180037)
[ عرض عادي ]
| 000 -LEADER | |
|---|---|
| fixed length control field | 09361namaa22004451i 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | EG-GICUC |
| 005 - أخر تعامل مع التسجيلة | |
| control field | 20260509133826.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 260509s2026 ua a|||frm||| 000 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Original cataloguing agency | EG-GICUC |
| Language of cataloging | eng |
| Transcribing agency | EG-GICUC |
| Modifying agency | EG-GICUC |
| Description conventions | rda |
| 041 0# - LANGUAGE CODE | |
| Language code of text/sound track or separate title | eng |
| Language code of summary or abstract | eng |
| -- | ara |
| 049 ## - Acquisition Source | |
| Acquisition Source | Deposit |
| 082 04 - DEWEY DECIMAL CLASSIFICATION NUMBER | |
| Classification number | 615.10846 |
| 092 ## - LOCALLY ASSIGNED DEWEY CALL NUMBER (OCLC) | |
| Classification number | 615.10846 |
| Edition number | 21 |
| 097 ## - Degree | |
| Degree | Ph.D |
| 099 ## - LOCAL FREE-TEXT CALL NUMBER (OCLC) | |
| Local Call Number | Cai01.08.09.Ph.D.2025.Sh.E |
| 100 0# - MAIN ENTRY--PERSONAL NAME | |
| Authority record control number or standard number | Sherif Sabry Abdel-Mageed, |
| Preparation | preparation. |
| 245 10 - TITLE STATEMENT | |
| Title | Exploratory mechanistic study of a novel antipsychotic drug in an experimental model of schizophrenia in rats / |
| Statement of responsibility, etc. | by Sherif Sabry Abdel-Mageed ; Supervision Dr. Helmy Moawad Sayed Ahmed, Dr. Safwat Abdelhady Mangoura, Dr. Ahmed Seifeldin Kamel. |
| 246 15 - VARYING FORM OF TITLE | |
| Title proper/short title | دراسة استقصائية لأليات عمل عقار مستحدث مضاد للذهان في نموذج تجريبي للفصام في الجرذان |
| 264 #0 - PRODUCTION, PUBLICATION, DISTRIBUTION, MANUFACTURE, AND COPYRIGHT NOTICE | |
| Date of production, publication, distribution, manufacture, or copyright notice | 2025. |
| 300 ## - PHYSICAL DESCRIPTION | |
| Extent | 156 pages : |
| Other physical details | illustrations ; |
| Dimensions | 25 cm. + |
| Accompanying material | CD. |
| 336 ## - CONTENT TYPE | |
| Content type term | text |
| Source | rda content |
| 337 ## - MEDIA TYPE | |
| Media type term | Unmediated |
| Source | rdamedia |
| 338 ## - CARRIER TYPE | |
| Carrier type term | volume |
| Source | rdacarrier |
| 502 ## - DISSERTATION NOTE | |
| Dissertation note | Thesis (Ph.D)-Cairo University, 2025. |
| 504 ## - BIBLIOGRAPHY, ETC. NOTE | |
| Bibliography, etc. note | Bibliography: pages 112-156. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | Schizophrenia (SCZ) is a complex, debilitating mental illness marked by cognitive deficits that impair functionality and quality of life. While traditional research has focused on dopaminergic and glutamatergic abnormalities in SCZ, emerging evidence highlights the crucial role of serotonergic dysregulation. Lumateperone (LUM), a recently FDA-approved atypical antipsychotic, exhibits a distinctive multimodal pharmacological profile characterized by combined antagonism of 5-HT2A and D2 receptors alongside serotonin reuptake inhibitory activity. This study investigated the procognitive effects of LUM mediated via 5-HT1A receptor activation in ketamine (Ket)-induced SCZ-like rat model. To this end, Male Wistar rats were administered 5 days Ket (30 mg/kg/day, i.p.), followed by LUM (10 mg/kg/day, p.o) for 14 days. To evaluate the proposed mechanistic pathway, a selective PI3K inhibitor (15 μg/kg/day, iv), Wortmannin (WM) was administered 30 minutes prior to LUM. Four days before the termination, animals underwent behavioral assessments, including the open field test, novel object recognition task, social interaction, Y-maze, and Morris water maze test. LUM restored hippocampal/cortical architecture, improved Ket-induced behavioral/cognitive deficits, reduced cortical CD86/GFAP, and increased CD163 immunoreactivity. Additionally, LUM decreased SERT activity and corrected the dysregulated expression of cortical 5-HT2A and hippocampal 5-HT1A receptors. LUM restored hippocampal 5-HT, 5-HIAA, and DA levels while amending cortical GAD67 and VGLUT1 immunoexpression. Alongside restoring PI3K/AKT/GSK-3β survival proteins and reinstating pCREB and BDNF levels. WM pre-administration nullified LUM’s effects, proving the involvement of the 5-HT1A/PI3K/Akt pathway. LUM demonstrates promising procognitive potential, offering insights into its therapeutic applications for cognitive dysfunction in SCZ. |
| 520 #3 - SUMMARY, ETC. | |
| Summary, etc. | الفُصَامُ هُوَ اضْطِرَابٌ عَقْلِيٌّ مُعَقَّدٌ وَمُنهِكٌ، يَتَمَيَّزُ بِوُجُودِ عُجْزٍ مَعْرِفِيٍّ يُضْعِفُ الأَدَاءَ الوَظِيفِيَّ وَنَوْعِيَّةَ الحَيَاةِ. وَفِيمَا تَرَكَّزَتِ البُحُوثُ التَّقْلِيدِيَّةُ عَلَى الِاضْطِرَابَاتِ فِي النِّظَامَيْنِ الدُّوبَامِينِيِّ وَالجلُوتَامَاتِيِّ فِي الفُصَامِ، تَظْهَرُ أَدِلَّةٌ حَدِيثَةٌ تُسَلِّطُ الضَّوْءَ عَلَى الدَّوْرِ الحَيَوِيِّ لاِخْتِلَالِ التَّنْظِيمِ السِّيرُوتُونِينِيِّ. يُعَدُّ لُومَاتِيبِيرُون، وَهُوَ مُضَادٌّ ذُهَانِيٌّ غَيْرُ نَمَطِيٍّ تَمَّتِ المُوَافَقَةُ عَلَيْهِ مُؤَخَّرًا مِنْ قِبَلِ إِدَارَةِ الغِذَاءِ وَالدَّوَاءِ الأَمْرِيكِيَّةِ، ذَا مِلَفٍّ دَوَائِيٍّ مُتَعَدِّدِ الآلِيَّاتِ، إِذْ يَجْمَعُ بَيْنَ الخَصَائِصِ المُضَادَّةِ لِمُسْتَقْبِلَاتِ 5-HT2A وَD2، إِضَافَةً إِلَى نَشَاطِهِ المُثَبِّطِ لِاسْتِرْجَاعِ السِّيرُوتُونِينِ. هَدَفَتْ هَذِهِ الدِّرَاسَةُ إِلَى تَحَرِّي التَّأْثِيرَاتِ المُعَزِّزَةِ لِلْوَظَائِفِ المَعْرِفِيَّةِ لِلوماتيبيرون، وَالمُتَوَسِّطَةِ مِنْ خِلَالِ تَنْشِيطِ مُسْتَقْبِلَاتِ 5-HT1A، وَذَلِكَ بِاسْتِخْدَامِ نَمُوذَجِ فِئْرَانٍ يُشْبِهُ الفُصَامَ تَمَّ تَحْفِيزُهُ بِاسْتِخْدَامِ الكِيتَامِين. وَلِتَحْقِيقِ هَذَا الهَدَفِ، تَمَّ إِعْطَاءُ ذُكُورِ فِئْرَانِ وَيِسْتَر جُرْعَةً مِنَ الكِيتَامِين (٣٠ مِجم/كجم/يَوْمِيًّا، داخل الصفاق) لِمُدَّةِ ٥ أَيَّامٍ، تَلَاهَا إِعْطَاءُ لوماتيبيرون (١٠ مِجم/كجم/يَوْمِيًّا، عَنْ طَرِيقِ الفَمِ) لِمُدَّةِ ١٤ يَوْمًا. وَلِتَقْيِيمِ المَسَارِ الآلِيِّ المُقْتَرَحِ، تَمَّ إِعْطَاءُ مُثَبِّطٍ اِنتِقَائِيٍّ لِإِنْزِيمِ PI3K وَهُوَ وُورْتْمَانِين (WM) بِجُرْعَةٍ (١٥ مِيكْرُوجرَام/كجم/يَوْمِيًّا، وِرِيدِيًّا) قَبْلَ ٣٠ دَقِيقَةً مِنْ إِعْطَاءِ لوماتيبيرون. قَبْلَ إِنْهَاءِ الدِّرَاسَةِ بِأَرْبَعَةِ أَيَّامٍ، خَضَعَتِ الحَيَوَانَاتُ لاِخْتِبَارَاتٍ سُلُوكِيَّةٍ، شَمِلَتِ اختِبَارَ الحَقْلِ المَفْتُوحِ، وَاختِبَارَ التَّعَرُّفِ عَلَى الأَجْسَامِ الجَدِيدَةِ، وَالتَّفَاعُلَ الاجْتِمَاعِيَّ، وَمَتَاهَةَ Y، وَمِتَاهَةَ مُورِيسَ المَائِيَّةَ. أَظْهَرَ لوماتيبيرون قُدْرَتَهُ عَلَى اِسْتِعَادَةِ البِنْيَةِ التَّشْرِيحِيَّةِ لِقرن أمون وَالقِشْرَةِ الدِّمَاغِيَّةِ، وَتَحْسِينِ العُجْزِ السُّلُوكِيِّ وَالمَعْرِفِيِّ النَّاتِجِ عَنِ الكِيتَامِين، وَتَقْلِيلِ مُسْتَوَيَاتِ CD86 وَGFAP فِي القِشْرَةِ، وَزِيَادَةِ التَّفَاعُلِ المَنَاعِيِّ لِـ CD163. كَمَا خَفَّضَ لوماتيبيرون نَشَاطَ نَاقِلِ السِّيرُوتُونِينِ (SERT)، وَصَحَّحَ التَّعْبِيرَ المُخْتَلَّ لِمُسْتَقْبِلَاتِ 5-HT2A القِشْرِيَّةِ وَ5-HT1A فِي الحُصَيْنِ. كَمَا أَعَادَ مُسْتَوَيَاتِ السِّيرُوتُونِينِ و 5-HIAAوَالدُّوبَامِينِ (DA) فِي قرن أمون، مَعَ تَعْدِيلِ التَّعْبِيرِ المَنَاعِيِّ لِـ GAD67 وَVGLUT1 فِي القِشْرَةِ. بِالإِضَافَةِ إِلَى ذَلِكَ، أَعَادَ تَنْظِيمَ بُرُوتِيناتِ البَقَاءِ PI3K/AKT/GSK-3β، وَاسْتَعَادَ مُسْتَوَيَاتِ كُلٍّ مِنْ pCREB وَBDNF. إِعْطَاءُ WM قَبْلَ لوماتيبيرون أَلْغَى تَأْثِيرَاتِهِ، مِمَّا يُثْبِتُ تَوَرُّطَ مَسَارِ 5-HT1A /PI3K/Akt فِي هَذِهِ الآلِيَّةِ. يُظهر لُوماتيبيرون قدرة واعدة في تعزيز الوظائف المعرفية، مما يوفر رؤى مهمة حول تطبيقاته العلاجية لاضطرابات الإدراك في الفُصام. |
| 530 ## - ADDITIONAL PHYSICAL FORM AVAILABLE NOTE | |
| Issues CD | Issues also as CD. |
| 546 ## - LANGUAGE NOTE | |
| Text Language | Text in English and abstract in Arabic & English. |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | Pharmacology |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| Topical term or geographic name entry element | الأدوية والسموم |
| 653 #1 - INDEX TERM--UNCONTROLLED | |
| Uncontrolled term | Schizophrenia-associated cognitive impairment |
| -- | Lumateperone |
| -- | 5-HT1A/2A receptors |
| -- | PI3k/Akt signaling |
| -- | Neuroinflammaion |
| -- | Hippocampus |
| -- | اضطراب الإدراك المرتبط بالفصام |
| -- | لوماتيبرون |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Helmy Moawad Sayed Ahmed |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Safwat Abdelhady Mangoura |
| Relator term | thesis advisor. |
| 700 0# - ADDED ENTRY--PERSONAL NAME | |
| Personal name | Ahmed Seifeldin Kamel |
| Relator term | thesis advisor. |
| 900 ## - Thesis Information | |
| Grant date | 01-01-2026 |
| Supervisory body | Helmy Moawad Sayed Ahmed |
| -- | Safwat Abdelhady Mangoura |
| -- | Ahmed Seifeldin Kamel |
| Universities | Cairo University |
| Faculties | Faculty of Pharmacy |
| Department | Department of Pharmacology |
| 905 ## - Cataloger and Reviser Names | |
| Cataloger Name | Shimaa |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | Dewey Decimal Classification |
| Koha item type | Thesis |
| Edition | 21 |
| Suppress in OPAC | No |
| Source of classification or shelving scheme | Home library | Current library | Date acquired | Inventory number | Full call number | Barcode | Date last seen | Effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|
| Dewey Decimal Classification | المكتبة المركزبة الجديدة - جامعة القاهرة | قاعة الرسائل الجامعية - الدور الاول | 09.05.2026 | 93988 | Cai01.08.09.Ph.D.2025.Sh.E | 01010110093988000 | 09.05.2026 | 09.05.2026 | Thesis |