Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease

Barlas, Orhan; CAN, Songül Meltem

doi:10.4274/BMB.galenos.2019.07.012

Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease

Songül Meltem CAN, (Sağlık Bilimleri Üniversitesi, Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi, Nöroşirürji Kliniği, İstanbul, Türkiye)

Orhan BARLAS (İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Nöroşirürji Anabilim Dalı, İstanbul, Türkiye)

Bağcılar Tıp Bülteni

2 1

Yıl: 2019 Cilt: 4 Sayı: 3 Sayfa Aralığı: 67 - 77 Metin Dili: İngilizce DOI: 10.4274/BMB.galenos.2019.07.012 İndeks Tarihi: 10-12-2020

Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease

Öz:

Objective: It is known that the acetylcholinergic afferents of the neocortex from subcortical areas participate in learning and memory. Autopsy studies in cases of Alzheimer’s disease (AD) have shown that most of the neurons of nucleus basalis magnocellularis (NBM) are atrophic or decreased in number. In this study, we searched for whether or not it was possible to improve the impaired learning and memory functions with foetal neural tissue transplantation in an experimental model of AD.Method: A total of thirty seven young adult male Wistar albino rats were served as experimental subjects. NBM on the right side was destroyed by the injection of kainic acid stereotactically so as to make a model of AD. The grafts were obtained from 14-16 day foetuses of the same genus. After the tissue with cholinergic neurons dissected from ventral forebrain and tissue with non-cholinergic neurons dissected from telencephalic vesicle, cell suspensions were prepared and injected stereotactically to the ipsilateral frontal cortex. Spatial learning and memory functions were tested by Morris’ water maze tasks.Results: Spatial learning and memory functions in rats were impaired by unilateral lesions of nucleus basalis magnocellularis. The impairment observed during the early period partially improved by the time. It was observed that this amelioration was accelerated with both cholinergic and non-cholinergic foetal neural tissue implantation. Conclusion: In our study, improvement of spatial learning and memory impairment with both cholinergic and non-cholinergic foetal neural tissue implantation can be explained by re-establishment of impaired connections via proliferation of limited number of surviving cholinergic neurons creating new synapses, as a result of upregulation of endogenous neural stem cells and activation of trophic mechanisms by implantation, rather than creation of functional synapses between the graft and the recipient tissue.

Anahtar Kelime:

Sıçanlarda Deneysel Alzheimer Hastalığı Modelinde Hacimsel Öğrenme ve Bellek Bozukluklarının Fetal Nöral Doku Transplantasyonu ile Düzelmesi

Öz:

Amaç: Subkortikal alanlardan neokortekse uzanan asetilkolinerjik nöronların öğrenme ve bellek süreçlerinde rol aldığı bilinmektedir. Alzheimer hastalığında (AH) yapılan otopsi incelemeleri bazal magnoselüler çekirdekteki nöronlarda atrofi veya azalma olduğunu göstermiştir. Bu çalışmada deneysel AH modelinde bozuk öğrenme ve bellek fonksiyonlarının, fötal nöral doku transplantasyonu ile düzelmesinin mümkün olup olmadığı araştırıldı. Yöntem: Deneysel çalışmada 37 adet Wistar albino cinsi genç erişkin erkek sıçan kullanıldı. AH modeli sağ bazal magnoselüler çekirdeğe stereotaktik yöntemle verilen, nörotoksik bir ajan olan kainik asit ile oluşturuldu. Greftler aynı cins sıçanların 14-16 günlük fetuslarından alındı. Kolinerjik nöronları içeren doku ventral ön beyinden, non-kolinerjik nöronların olduğu doku ise telensefalik vezikülden elde edilerek, hücre süspansiyonu haline getirildi ve stereotaktik yöntemle ipsilateral frontal kortekse implante edildi. Hacimsel öğrenme ve bellek fonksiyonları Morris’in “water maze” testi ile değerlendirildi. Bulgular: Tek taraflı bazal magnoselüler nükleus lezyonları ile sıçanlarda hacimsel öğrenme ve bellek fonksiyonları bozuldu. Erken dönemde bozulan bu fonksiyonlar geç dönemde kısmen düzeldi. Hem kolinerjik hem de non-kolinerjik fötal doku implantasyonu ile bu düzelmenin hızlandığı saptandı. Sonuç: Çalışmamızda hem kolinerjik hem de non-kolinerjik fötal nöral doku implantasyonu ile hacimsel öğrenme ve bellek fonksiyonlarının düzelmesi, greftin alıcı doku ile fonksiyonel sinapslar oluşturmasından ziyade, implantasyonun endojen nöral kök hücrelerini regüle etmesi ve trofik mekanizmaları harekete geçirmesi sonucu, sağ kalan az sayıdaki kolinerjik nöronların çoğalması ve yeni sinapslar oluşturarak bozulmuş bağlantıları yeniden kurması ile açıklanabilir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	CAN S, Barlas O (2019). Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. , 67 - 77. 10.4274/BMB.galenos.2019.07.012
Chicago	CAN Songül Meltem,Barlas Orhan Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. (2019): 67 - 77. 10.4274/BMB.galenos.2019.07.012
MLA	CAN Songül Meltem,Barlas Orhan Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. , 2019, ss.67 - 77. 10.4274/BMB.galenos.2019.07.012
AMA	CAN S,Barlas O Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. . 2019; 67 - 77. 10.4274/BMB.galenos.2019.07.012
Vancouver	CAN S,Barlas O Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. . 2019; 67 - 77. 10.4274/BMB.galenos.2019.07.012
IEEE	CAN S,Barlas O "Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease." , ss.67 - 77, 2019. 10.4274/BMB.galenos.2019.07.012
ISNAD	CAN, Songül Meltem - Barlas, Orhan. "Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease". (2019), 67-77. https://doi.org/10.4274/BMB.galenos.2019.07.012

APA	CAN S, Barlas O (2019). Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. Bağcılar Tıp Bülteni, 4(3), 67 - 77. 10.4274/BMB.galenos.2019.07.012
Chicago	CAN Songül Meltem,Barlas Orhan Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. Bağcılar Tıp Bülteni 4, no.3 (2019): 67 - 77. 10.4274/BMB.galenos.2019.07.012
MLA	CAN Songül Meltem,Barlas Orhan Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. Bağcılar Tıp Bülteni, vol.4, no.3, 2019, ss.67 - 77. 10.4274/BMB.galenos.2019.07.012
AMA	CAN S,Barlas O Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. Bağcılar Tıp Bülteni. 2019; 4(3): 67 - 77. 10.4274/BMB.galenos.2019.07.012
Vancouver	CAN S,Barlas O Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease. Bağcılar Tıp Bülteni. 2019; 4(3): 67 - 77. 10.4274/BMB.galenos.2019.07.012
IEEE	CAN S,Barlas O "Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease." Bağcılar Tıp Bülteni, 4, ss.67 - 77, 2019. 10.4274/BMB.galenos.2019.07.012
ISNAD	CAN, Songül Meltem - Barlas, Orhan. "Improvement of Spatial Learning and Memory Impairments by Fetal Neural Tissue Transplantation in Experimental Rat Model of Alzheimer’s Disease". Bağcılar Tıp Bülteni 4/3 (2019), 67-77. https://doi.org/10.4274/BMB.galenos.2019.07.012