آثار طويلة المدى للسكوبولامين على أنسجة المخ لدى الفئران
DOI:
https://doi.org/10.32007/jfacmedbaghdad.6632323الكلمات المفتاحية:
Alzheimer’s disease، Antioxidant، Cognitive function، Oxidative stress، Scopolamineالملخص
خلفية البحث: السكوبولامين هو دواء مضاد للكولين يعطل انتقال الكوليني في الجهاز العصبي المركزي كما أنه يسبب تشوهات إدراكية وعلامات مرضية مشابهة لتلك التي تظهر في مرض الزهايمر. ولذلك، يتم استخدامه لتحريض مرض الزهايمر في النماذج الحيوانية.
الأهداف: كان الهدف من الدراسة الحالية هو دراسة آثار التحريض طويل المدى مع السكوبولامين على أنسجة المخ لدى الفئران.
طرق العمل: تم تقسيم سبعين فأراً بالغاً إلى مجموعتين متساويتين: المجموعة الأولى كانت مجموعة طبيعية ومراقبة تلقت الماء المقطر فقط. أما المجموعة الثانية فكانت مجموعة تحريض مرض الزهايمر حيث تلقت السكوبولامين داخل الصفاق (1 ملجم / كجم) لمدة 14 يومًا فقط بعد ذلك تم إعطاء الماء المقطر لمدة 6 أشهر التالية. تم عزل عشرة فئران من كل مجموعة في وقت الصفر، بعد أسبوعين من التحريض، وبعد 3 أشهر وبعد 6 أشهر، وتم إخضاعها للاختبارات السلوكية ثم تم تشريحها لتحديد العوامل البيوكيميائية (بما في ذلك عامل التغذية العصبية المشتق من الدماغ، وحالة مضادات الأكسدة الكلية، والمالونديالدهيد). والأميلويد β) ولفحص الأنسجة المرضية لأنسجة المخ. وقد تم تحليل البيانات باستخدام اختبارات t، وANOVA. مع اعتبار جميع القيم المعبر عنها كقيمة متوسط ± SD وقيمة P <0.05 ذات دلالة احصائية.
النتائج: أنتج السكوبولامين تغيرات نسيجية مرضية في الدماغ مشابهة لتلك التي تحدث في مرض الزهايمر البشري. ومع ذلك، لم تنتج فروق ذات دلالة إحصائية أخرى في الاختبار السلوكي، والعلامات البيوكيميائية، و/أو السمات المرضية النسيجية خلال الفترة الإجمالية للدراسة.
الاستنتاجات: يُحدث السكوبولامين تغيرات في أنسجة المخ والتي تستمر لفترة طويلة ويمكن استخدامه لدراسة مرض الزهايمر على المدى الطويل.
التنزيلات
المراجع
Cheon SY, Koo B-N, Kim SY, Kam EH, Nam J, Kim EJ. Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice. Scientific Reports. 2021;11(1):8376.
https://doi.org/10.1038/s41598-021-87790-y.
Chen WN, Yeong KY. Scopolamine, a toxin-induced experimental model, used for research in Alzheimer’s disease. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2020;19(2):85-93. https://doi.org/10.2174/1871527319666200214104331.
Yadang FSA, Nguezeye Y, Kom CW, Betote PHD, Mamat A, Tchokouaha LRY, et al. Scopolamine-induced memory impairment in mice: neuroprotective effects of Carissa edulis (Forssk.) Valh (Apocynaceae) aqueous extract. International Journal of Alzheimer’s Disease. 2020;2020. https://doi.org/10.1155/2020/6372059.
Rahimzadegan M, Soodi M. Comparison of memory impairment and oxidative stress following single or repeated doses administration of scopolamine in rat hippocampus. Basic and clinical neuroscience. 2018;9(1):5. https://doi.org/10.29252/NIRP.BCN.9.1.5.
Hernández-Rodríguez M, Arciniega-Martínez IM, García-Marín ID, Correa-Basurto J, Rosales-Hernández MC. Chronic administration of scopolamine increased GSK3βP9, beta secretase, amyloid beta, and oxidative stress in the hippocampus of Wistar rats. Molecular Neurobiology. 2020;57:3979-88. https://doi.org/10.1007/s12035-020-02009-x.
Mahdi O, Baharuldin MTH, Nor NHM, Chiroma SM, Jagadeesan S, Moklas MAM. Chemicals used for the induction of Alzheimer’ s disease-like cognitive dysfunctions in rodents. Biomedical Research and Therapy. 2019;6(11):3460-84. https://doi.org/10.15419/bmrat.v6i11.575.
Pitts MW. Barnes maze procedure for spatial learning and memory in mice. Bio-protocol. 2018;8(5):e2744-e. https://doi.org/10.21769/BioProtoc.2744.
Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. JoVE (Journal of Visualized Experiments). 2017(126):e55718. https://doi.org/10.3791/55718.
Prieur EA, Jadavji NM. Assessing spatial working memory using the spontaneous alternation Y-maze test in aged male mice. Bio-protocol. 2019; 9 (3): e3162-ed https://doi.org/10.21769/BioProtoc.3162.
Kirkwood BR, Sterne JA. Essential medical statistics: John Wiley & Sons; 2010.
DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Molecular neurodegeneration. 2019;14(1):1-18. https://doi.org/10.1186/s13024-019-0333-5.
Miller JA, Horvath S, Geschwind DH. Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways. Proceedings of the National Academy of Sciences. 2010;107(28):12698-703. https://doi.org/10.1073/pnas.0914257107
Radulescu CI, Cerar V, Haslehurst P, Kopanitsa M, Barnes SJ. The aging mouse brain: cognition, connectivity and calcium. Cell Calcium. 2021;94:102358. https://doi.org/10.1016/j.ceca.2021.102358.
Shoji H, Miyakawa T. Age‐related behavioral changes from young to old age in male mice of a C57 BL/6J strain maintained under a genetic stability program. Neuropsychopharmacology reports. 2019;39(2):100-18. https://doi.org/10.1002/npr2.12052
Hendrickx JO, De Moudt S, Calus E, De Deyn PP, Van Dam D, De Meyer GR. Age-related cognitive decline in spatial learning and memory of C57BL/6J mice. Behavioural brain research. 2022; 418: 113649. https://doi.org/10.1016/j.bbr.2021.113649.
Crespo NE. Age-Related Cognitive Decline in Female C57BL/6cenp Mice 15-16 Months of Age. J Biomed Eng. 2021; 5: 1-12. https://doi.org/10.17303/jber.2021.5.101.
Clifford KP, Miles AE, Prevot TD, Misquitta KA, Ellegood J, Lerch JP, et al. Brain structure and working memory adaptations associated with maturation and aging in mice. Frontiers in Aging Neuroscience. 2023; 15. https://doi.org/10.3389/fnagi.2023.1195748.
Chi H, Chang H-Y, Sang T-K. Neuronal cell death mechanisms in major neurodegenerative diseases. International journal of molecular sciences. 2018; 19 (10): 3082. https://doi.org/10.3390/ijms19103082.
Janssen L, Keppens C, De Deyn PP, Van Dam D. Late age increase in soluble amyloid-beta levels in the APP23 mouse model despite steady-state levels of amyloid-beta-producing proteins. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2016;1862(1):105-12. https://doi.org/10.1016/j.bbadis.2015.10.027.
Ameen-Ali KE, Simpson JE, Wharton SB, Heath PR, Sharp PS, Brezzo G, et al. The time course of recognition memory impairment and glial pathology in the hAPP-J20 mouse model of Alzheimer’s disease. Journal of Alzheimer's Disease. 2019;68(2):609-24.https://doi.org/10.3233/JAD181238.
Endres T, Lessmann V. Age-dependent deficits in fear learning in heterozygous BDNF knock-out mice. Learning & memory. 2012;19(12):561-70. http://www.learnmem.org/cgi/doi/10.1101/lm.028068.112.
Psotta L, Lessmann V, Endres T. Impaired fear extinction learning in adult heterozygous BDNF knock-out mice. Neurobiology of learning and memory. 2013;103:34-8.
https://doi.org/10.1016/j.nlm.2013.03.003
Harb M, Jagusch J, Durairaja A, Endres T, Leßmann V, Fendt M. BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment. Translational Psychiatry. 2021;11(1):233. https://doi.org/10.1038/s41398-021-01365-z.
Cases S, Saavedra A, Tyebji S, Giralt A, Alberch J, Pérez-Navarro E. Age-related changes in STriatal-Enriched protein tyrosine Phosphatase levels: Regulation by BDNF. Molecular and Cellular Neuroscience. 2018;86:41-9. https://doi.org/10.1016/j.mcn.2017.11.003.
Walker MP, LaFerla FM, Oddo SS, Brewer GJ. Reversible epigenetic histone modifications and Bdnf expression in neurons with aging and from a mouse model of Alzheimer’s disease. Age. 2013;35:519-31. https://doi.org/10.1007/s11357-011-9375-5.
Ceballos-Picot I, Nicole A, Clément M, Bourre J-M, Sinet P-M. Age-related changes in antioxidant enzymes and lipid peroxidation in brains of control and transgenic mice overexpressing copper-zinc superoxide dismutase. Mutation Research/DNAging. 1992;275(3-6):281-93. https://doi.org/10.1016/0921-8734(92)90032-k.
Leyane TS, Jere SW, Houreld NN. Oxidative stress in ageing and chronic degenerative pathologies: molecular mechanisms involved in counteracting oxidative stress and chronic inflammation. International journal of molecular sciences. 2022;23(13):7273. https://doi.org/10.3390/ijms23137273.
Heurtaux T, Bouvier DS, Benani A, Helgueta Romero S, Frauenknecht KB, Mittelbronn M, et al. Normal and pathological NRF2 signalling in the central nervous system. Antioxidants. 2022;11(8):1426. https://doi.org/10.3390/antiox11081426 .
Illes P, Rubini P, Ulrich H, Zhao Y, Tang Y. Regulation of microglial functions by purinergic mechanisms in the healthy and diseased CNS. Cells. 2020;9(5):1108. https://doi.org/10.3390/cells9051108.
Woo Y, Lim JS, Oh J, Lee JS, Kim J-S. Neuroprotective effects of euonymus alatus extract on scopolamine-induced memory deficits in mice. Antioxidants. 2020; 9 (5) :449. https://doi.org/10.3390/antiox9050449.
Cheedella HK, Silakabattini K, Siahmansur TJ, Ishaq BM. Evaluation Of Neuroprotective Activity In Scopolamine Induced Dementia In Wistar Rats By Using Various Pharmacological Equipment And Its Histopathology. Journal of Survey in Fisheries Sciences. 2023: 1299-307. https://sifisheriessciences.com/index.php/journal/article/view/813/363.
Lee JC, Park JH, Ahn JH, Park J, Kim IH, Cho JH, et al. Effects of chronic scopolamine treatment on cognitive impairment and neurofilament expression in the mouse hippocampus. Molecular medicine reports. 2018;17(1):1625-32. https://doi.org/10.3892/mmr.2017.8082
Kim JH, Han Y-E, Oh S-J, Lee B, Kwon O, Choi CW, et al. Enhanced neuronal activity by suffruticosol A extracted from Paeonia lactiflora via partly BDNF signaling in scopolamine-induced memory-impaired mice. Scientific Reports. 2023;13(1):11731. https://doi.org/10.1038/s41598-023-38773-8.
Ban JY, Park HK, Kim SK. Effect of glycyrrhizic acid on scopolamine-induced cognitive impairment in mice. International Neurourology Journal. 2020;24(Suppl 1):S48. https://doi.org/10.5213/inj.2040154.077.
Bae HJ, Sowndhararajan K, Park H-B, Kim S-Y, Kim S, Kim DH, et al. Danshensu attenuates scopolamine and amyloid-β-induced cognitive impairments through the activation of PKA-CREB signaling in mice. Neurochemistry International. 2019;131:104537. https://doi.org/10.1016/j.neuint.2019.104537.
Aykac A, Ozbeyli D, Uncu M, Ertaş B, Kılınc O, Şen A, et al. Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors. Gene. 2019; 689:194-201. https://doi.org/10.1016/j.gene.2018.12.007.
Anand A, Khurana N, Ali N, AlAsmari AF, Alharbi M, Waseem M, et al. Ameliorative effect of vanillin on scopolamine-induced dementia-like cognitive impairment in a mouse model. Frontiers in Neuroscience. 2022;16:1005972. https://doi.otg/10.3389/fnins.2022.1005972.
Lee M-R, Yun B-S, Park S-Y, Ly S-Y, Kim S-N, Han B-H, et al. Anti-amnesic effect of Chong–Myung–Tang on scopolamine-induced memory impairments in mice. Journal of ethnopharmacology. 2010;132(1):70-4. https://doi.org/10.1016/j.jep.2010.07.041
Sharma C, Kim SR. Linking oxidative stress and proteinopathy in Alzheimer’s disease. Antioxidants. 2021;10(8):1231. https://doi.org/10.3390/antiox10081231
التنزيلات
منشور
إصدار
القسم
الرخصة
الحقوق الفكرية (c) 2024 Neven N. Istifo, Mohammed A. AL- Zobaidy, Kasim S. Abass
هذا العمل مرخص بموجب Creative Commons Attribution 4.0 International License.
Creative Commons Attribution 4.0 International license..
