anadolu klin Anatolian Clinic the Journal of Medical Sciences 2149-5254 2458-8849 Hayat Sağlık ve Sosyal Hizmetler Vakfı 10.21673/anadoluklin.1062913 Health Care Administration Sağlık Kurumları Yönetimi Sıçanlarda 6-hidroksidopamin modeli ile oluşturulan Parkinson hastalığında valproik asit tedavisinin dopaminerjik nöronal kayıp üzerindeki anti-apoptotik etkileri Anti-apoptotic effects of valproic acid treatment on dopaminergic neuronal loss in a 6-hydroxydopamine model of Parkinson’s disease in rats https://orcid.org/0000-0002-9491-8220 Cumbul Alev YEDITEPE UNIVERSITY, SCHOOL OF MEDICINE https://orcid.org/0000-0002-0253-2217 Eyuboglu Signem ISTINYE UNIVERSITY, SCHOOL OF MEDICINE https://orcid.org/0000-0002-9788-1101 Keleş Elif Çiğdem YEDITEPE UNIVERSITY, SCHOOL OF MEDICINE https://orcid.org/0000-0003-3953-7131 Uslu Unal ISTANBUL MEDENIYET UNIVERSITY, SCHOOL OF MEDICINE https://orcid.org/0000-0002-2479-1236 Genç Ece YEDITEPE UNIVERSITY, SCHOOL OF MEDICINE 05 24 2022 27 2 194 203 01 25 2022 03 13 2022 Copyright © 1933, Anadolu Kliniği Tıp Bilimleri Dergisi 1933 Anadolu Kliniği Tıp Bilimleri Dergisi

Amaç: Parkinson hastalığı (PH), hastalarda motor aktivitede bozulma ile sonuçlanan dopaminerjik nöronlarınilerleyici kaybı ile karakterizedir. Levodopa (L-DOPA) dâhil olmak üzere mevcut tedaviler daha çok semptomların tedavisine yöneliktir. Bu nedenle, etkili nöroprotektif tedavilerin geliştirilmesine ihtiyaç vardır. Valproik asit (VPA), çeşitli beyin bölgelerindeki dopamin (DA) nöronları üzerinde güçlü nöroprotektif etkiler göstermiştir. Bu çalışmanın amacı, sıçanlarda 6-hidroksidopamin (6-OHDA) ile indüklenen PH modelinde VPA’nın L-DOPA ile birlikte tedavi edildiğinde nöronal kaybı azaltıp azaltmadığını araştırmaktır.Yöntemler: Erkek Wistar Albino sıçanlarına tek taraflı olarak intranigral 6-OHDA enjeksiyonu yapıldı. On iki gün sonra sıçanlara, 9 gün boyunca salin, L-DOPA, VPA veya L-DOPA+ VPA verildi. Sıçanlarda dopaminerjik nöron kaybı olup olmadığını belirlemek için apomorfin kaynaklı rotasyon testi kullanıldı. Substantia Nigra pars compacta’da (SNpc) tirozin hidroksilaz (TH) pozitif nöronlar ve apoptotik nöronlar ölçümleri için immünohistokimyasal analizler yapıldı.Bulgular: 6-OHDA enjeksiyonu, klinik motor fonksiyon bozukluğu ve dopaminerjik nöronlarda önemli hasar gösterdi. VPA tedavisi, TH pozitif nöronları artırarak ve apoptotik nöronları azaltarak SNpc’deki nöronları korumuştur. L-DOPA ise bu parametreler üzerinde etkisizdi.Sonuç: Deneylerimiz, PH sıçan modelinde L-DOPA ile birlikte kullanıldığında VPA’nın nöroprotektif bir etkiye sahip olduğunu göstermiştir.

Aim: Parkinson’s disease (PD) is characterized by the progressive loss of dopaminergic neurons resulting in deterioration of motor activity in patients. Currently, available therapies including Levodopa (L-DOPA) are more geared toward the treatment of symptoms. Therefore, developing effective neuroprotective therapies is needed. Valproic acid (VPA) has shown potent neuroprotective effects on dopamine (DA) neurons in various brain regions. The aim of this study is to investigate whether VPA attenuates the neuronal loss when co-treated with L-DOPA in a 6-hydroxydopamine (6-OHDA) induced PD model in rats.Methods: Male Wistar Albino rats received intranigral injection of 6-OHDA unilaterally. Twelve days later rats received either saline, L-DOPA, VPA, or L-DOPA+ VPA for 9 days. To determine whether rats had dopaminergic neuronal loss apomorphine-induced rotation test was used. Immunohistochemical analyses were performed in the Substantia Nigra pars compacta (SNpc) by measuring the tyrosine hydroxylase (TH) positive neurons and the apoptotic neurons.Results: 6-OHDA injection showed clinically impairment of the motor function with histologically significant damage to the dopaminergic neurons. VPA administration combined with L- DOPA protected neurons in SNpc by increasing the TH positive neurons and by decreasing the apoptotic neurons. L-DOPA given as a monotherapy, on the other hand, was ineffective on these parameters.Conclusion: Our experiments demonstrated that VPA had a neuroprotective effect when used with L-DOPA in the PD rat model.

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