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Yıl:2014; Cilt: 1; Sayı: 3>> Özet
TAM METİN
The Journal of Neurobehavioral Sciences; 2014;1(3):72-76
Şizofreniyi Anlamakta Alternatif Bir Yaklaşım: NMDA Reseptörleri Aracılığı İle Poliamin Hipotezi
T Uzbay
Üsküdar Üniversitesi, İstanbul
Şizofrenide glutamat hipotezi N-metil-D-aspartat (NMDA) reseptör antagonistlerinin insanlarda ve deney hayvanlarda şizofreni semptomları oluşturmasına dayanır. Anormal glutamaterjik iletinin şizofreninin bilişsel, pozitif ve negative semptomları ile ilişkisine işaret eden birçok kanıt vardır ve glutamaterjik sistem şizofreni tedavisinde yeni ilaçların geliştirilmesi için güncel ve önemli bir odaktır. Poliaminler doğada ve canlı organizmalarda yaygın olarak bulunan putresin, spermidin, spermin ve agmatin gibi birden fazla amin içeren alifatik moleküllerdir. Poliaminler ve bunların biyosentetik enzimleri vücutta merkezi sinir sistemi de (MSS) dâhil olmak üzere yaygın olarak bulunur. Poliaminler hücre büyümesinin modülasyonu ve hücre membran işlevlerinde önemli bir role sahiptir. Şizofreninin sinir hücresi membranlarındaki genel bir anomalite ile ilişkili olduğu hipotezi ileri sürülmüştür. Bir poliamin olan agmatin sıçan hipokampal nöronlarında glutamaterjik NMDA reseptörlerini seçici bir şekilde bloke eder. Poliaminlerle şizofreni hastalığının etyopatogenezi arasında ilişkiye işaret eden çeşitli kanıtlar da mevcuttur. Bu gözden geçirme yazısında biyolojik aktif bir nörotransmitter olan agmatin ile NMDA reseptörleri arasındaki etkileşme üzerinden şizofreninin anlaşılmasına yönelik yeni bir yaklaşım ileri sürülmektedir.
An Alternative Approach to Understand Schizophrenia: Polyamines Hypothesis through NMDA Receptors
The glutamate hypothesis of schizophrenia based on the observations that administration of drugs that block N-methyl-D-aspartate (NMDA) glutamate receptors could induce schizophrenia-like symptoms. There are several evidences linking abnormal glutamatergic transmission to cognitive, negative, and positive symptoms of schizophrenia and the glutamatergic system is now a major focus for the development of new compounds in schizophrenia. The polyamines are omnipresent aliphatic molecules comprising putrescine, spermidine, spermine and agmatine. The polyamines and their biosynthetic enzymes are found throughout the body, including the central nervous system (CNS), where they display specific regional distributions in the CNS. The polyamines have an important role in the modulation of cell growth and on cell membrane functions. It was hypothesized that schizophrenia may be related to a general abnormality in neuronal membranes. Agmatine, a polyamine, selectively blocks the NMDA subclass of glutamate receptors in rat hippocampal neurons. There are also several evidences indicate that a relationship between polyamines and etiopathogenesis of schizophrenia. In this review, a new approach for understanding schizophrenia via NMDA receptors and their interaction with agmatine which is a biological active polyamine transmitter in brain is proposed.

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