Sıçanlarda deneysel Alzheimer tipi demans modelinde yeni bir nörotrofik molekül olan nöritinin rolü
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Tarih
2022
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Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Alzheimer hastalığı (AH), günlük yaşamsal aktivitelerde azalma ve bilişsel yeteneklerde
bozulma ile karakterize, nöropsikiyatrik semptomların ve davranış değişikliklerinin eşlik ettiği
nörodejeneratif bir hastalıktır. AH demansın en sık görülen tipi olup prevalansı gün geçtikçe
artmaktadır. Fizyopatolojisinde oluşan anormal amiloit prekursor proteinler (APP), hücre içinde
nörofibril yumakları (NFY) ve senil plaklar (SP) birikmesi, sinir hücrelerinde sinaptik iletimin
kaybına ve özellikle hipokampus ve serebral korteksteki nöronların ölümüne yol açmaktadır.
Asetil kolin (ACh) hipokampusu serebral kortekse bağlayan nörotransmitterdir. Kolin ve
asetil koA’dan ‘asetil transferaz’ enzimi ile ‘asetil kolin’ oluşur. AH’de primer defisit beyindeki
kolinerjik sistemin, özellikle öğrenme ve bellek ile ilgili bölgelerde, bozulmasıdır.
Plastisite geni 15 (CPG 15) olarak da bilinen nöritin, aktivite ile indüklenen
glikozilfosfatidilinozitol bağımlı bir aksonal protein olup çoğunlukla merkezi sinir sisteminde
eksprese edilir. İlk olarak ratların dentat girusunda, daha sonra insanda tespit edilmiştir. Nötirinin
hafızayı etkileyen nörodejeneratif ve nöropsikolojik hastalıklarda da rol oynayabileceği ileri
sürülmüştür. Sinirsel gelişim ve sinaptik plastisitedeki çok yönlü rolleriyle nöritin, MSS’nin nöronal
bağlantılarının yeniden oluşmasında katkı sağlar.
Deneysel AH modelleri birçok araştırmada AH etiyofizyopatolojisinin anlaşılması ve
potansiyel tedavi seçeneklerinin etkinliğinin belirlenmesine yönelik olarak son yıllarda yoğun olarak
kullanılmaktadır. Bu bağlamda MSS’de eksprese edilen yeni bir molekül olan nöritin (NRN),
nörodejeneratif hastalıklarda araştırılan ümit verici bir peptittir. AH süreçlerinde NRN etkisini konu
alan oldukça sınırlı sayıda araştırma bulgusu yer almaktadır. Nöritinin sıçanlardaki olası etkinliğinin
davranış modelleri ve nöronal moleküler belirteçler düzeyinde etkisi ise araştırılmamıştır. Bu nedenle
mevcut çalışmamızda yeni bir nörotrofik molekül olan NRN’nin AH’deki olası nöroprotektif
etkinliğinin araştırılması amaçlanmıştır.
Çalışmada 40 adet erkek sıçan Kontrol, demans, nöritin, demans + nöritin grupları olarak 4
gruba ayrılmıştır. Tüm hayvanlara anestezi altında stereotaksik cihaz ile ozmotik minipompa
yerleştirilmiştir. Demans gruplarına streptozotosin intraserebroventriküler (İSV) yolla enjekte
edilmiştir. Nöritin ve çözücüsü İSV yolla 7 gün boyunca infüze edilmiştir. 8. günde sıçanlara davranış
testleri uygulanmıştır. Morris’in su labirenti testinde (MST) her bir hayvanın performansı
kaydedilerek davranış parametreleri değerlendirilmiştir. Tüm sıçanlardan elde edilen serum ve beyin
dokuları toplanmış ve ELISA yöntemiyle hipokampal kolinerjik aktivite analizleri gerçekleştirilmiştir.
MST bulgularında NRN uygulanan gruplarda demans gruplarına kıyasla platformu bulma
süresi, platforma yüzme mesafesi ve hızı açısından istatistiksel olarak olumlu sonuçlar elde edilmiştir.
Moleküler analiz sonuçları istatistiksel olarak anlamlı olmasa da tedavi grubunda ChAT aktivitesinde
artış tespit edilmiştir.
Çalışma bulgularımız, NRN’nin AH tedavisi üzerine olan etkilerinin araştırıldığı
derinlemesine çalışmaların, AH için yeni bir tedavi seçeneği olarak NRN’nin etkinliği konusunda yeni
ufuklar açacağını düşündürmektedir.
Alzheimer's disease (AD) has a degenerative view from the part of training, neuropsychiatric education and training with use and equipment in daily life use. AD is the most common manifestation of dementia and its prevalence is increasing day by day. Neurofibrillary tangles (NFT) and senile plaques (SP) within a cell formed in its physiopathology are considered to be acquired pathways and are detached from targets in the cerebral cortex. Acetylcholine (ACh) is the neurotransmitter that connects the hippocampus to the cerebral cortex. Acetyl choline is formed by the enzyme 'acetyl transferase' from choline and acetyl coA. The primary deficit in AD is the disruption of the cholinergic system in the brain, especially in regions related to learning and memory. Neuritin, also known as plasticity gene 15 (CPG 15), is an activity-induced glycosylphosphatidylinositol-dependent axonal protein and is mostly expressed in the central nervous system. It was first detected in the dentate gyrus of rats and later in humans. It has been suggested that neutirine may also play a role in neurodegenerative and neuropsychological diseases that affect memory. With its versatile roles in neural development and synaptic plasticity, neuritin contributes to the regeneration of neuronal connections of the CNS. Experimental AD models have been used extensively in many studies in recent years to understand the etiophysiopathology of AD and to determine the effectiveness of potential treatment options. In this context, neuritin (NRN), a new molecule expressed in the CNS, is a promising peptide investigated in neurodegenerative diseases. There are very limited research findings on the effect of NRN in AD processes. The possible effect of neuritis in rats at the level of behavioral patterns and neuronal molecular markers has not been investigated. Therefore, in our current study, it was aimed to investigate the possible neuroprotective activity of NRN, a new neurotrophic molecule, in AD. In the study, 40 male rats were divided into 4 groups as control, dementia, neuritin, dementia + neuritin groups. All animals were placed under anesthesia with a stereotaxic device and an osmotic minipump. Streptozotocin was injected intracerebroventricularly (ICV) to dementia groups. Neuritin and its solvent were infused by ISV for 7 days. Behavioral tests were applied to the rats on the 8th day. In Morris' water maze test (MWM), the performance of each animal was recorded and behavioral parameters were evaluated. Serum and brain tissues obtained from all rats were collected and hippocampal cholinergic activity analyzes were performed by ELISA method. In the MST findings, statistically positive results were obtained in terms of time to find the platform, swimming distance to the platform and speed in the NRN applied groups compared to the dementia groups. Although the results of the molecular analysis were not statistically significant, an increase in ChAT activity was detected in the treatment group. Our study findings suggest that in-depth studies investigating the effects of NRN on the treatment of AD will open new horizons for the effectiveness of NRN as a new treatment option for AD.
Alzheimer's disease (AD) has a degenerative view from the part of training, neuropsychiatric education and training with use and equipment in daily life use. AD is the most common manifestation of dementia and its prevalence is increasing day by day. Neurofibrillary tangles (NFT) and senile plaques (SP) within a cell formed in its physiopathology are considered to be acquired pathways and are detached from targets in the cerebral cortex. Acetylcholine (ACh) is the neurotransmitter that connects the hippocampus to the cerebral cortex. Acetyl choline is formed by the enzyme 'acetyl transferase' from choline and acetyl coA. The primary deficit in AD is the disruption of the cholinergic system in the brain, especially in regions related to learning and memory. Neuritin, also known as plasticity gene 15 (CPG 15), is an activity-induced glycosylphosphatidylinositol-dependent axonal protein and is mostly expressed in the central nervous system. It was first detected in the dentate gyrus of rats and later in humans. It has been suggested that neutirine may also play a role in neurodegenerative and neuropsychological diseases that affect memory. With its versatile roles in neural development and synaptic plasticity, neuritin contributes to the regeneration of neuronal connections of the CNS. Experimental AD models have been used extensively in many studies in recent years to understand the etiophysiopathology of AD and to determine the effectiveness of potential treatment options. In this context, neuritin (NRN), a new molecule expressed in the CNS, is a promising peptide investigated in neurodegenerative diseases. There are very limited research findings on the effect of NRN in AD processes. The possible effect of neuritis in rats at the level of behavioral patterns and neuronal molecular markers has not been investigated. Therefore, in our current study, it was aimed to investigate the possible neuroprotective activity of NRN, a new neurotrophic molecule, in AD. In the study, 40 male rats were divided into 4 groups as control, dementia, neuritin, dementia + neuritin groups. All animals were placed under anesthesia with a stereotaxic device and an osmotic minipump. Streptozotocin was injected intracerebroventricularly (ICV) to dementia groups. Neuritin and its solvent were infused by ISV for 7 days. Behavioral tests were applied to the rats on the 8th day. In Morris' water maze test (MWM), the performance of each animal was recorded and behavioral parameters were evaluated. Serum and brain tissues obtained from all rats were collected and hippocampal cholinergic activity analyzes were performed by ELISA method. In the MST findings, statistically positive results were obtained in terms of time to find the platform, swimming distance to the platform and speed in the NRN applied groups compared to the dementia groups. Although the results of the molecular analysis were not statistically significant, an increase in ChAT activity was detected in the treatment group. Our study findings suggest that in-depth studies investigating the effects of NRN on the treatment of AD will open new horizons for the effectiveness of NRN as a new treatment option for AD.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Alzheimer Hastalığı, Nöritin, Öğrenme ve Bellek, Alzheimer's Disease, Neuritin, Learning and Memory
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Özkürkçüler, A. (2022). Sıçanlarda deneysel Alzheimer tipi demans modelinde yeni bir nörotrofik molekül olan nöritinin rolü. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Fizyoloji Anabilim Dalı, Konya.
