Ionotropic Glutamate Receptor Expression in the Hypothalamus: An Immunohistochemical Localization Study

Abstract

major excitatory amino acid neurotransmitter in the hypothalamus. Glutamate performs its regulatory function on neurons by binding to its receptors, which are classified in two subfamilies as ionotropic and metabotropic. It has been determined by electrophysiological and pharmacological studies that glutamate is effective on some neuroendocrine neurons. Due to the lack of studies supporting glutamatergic innervation histomorphologically, our study focused on hypothalamic glutamate receptor subunits. The distributions of AMPA (GluA1, GluA2, GluA3, GluA4), kainic acid (GluK5, GluK1, GluK2, GluK3) and NMDA (GluN1, GluN2A) in the hypothalamus, which are ionotropic glutamate receptor subunits, were investigated using the immunohistochemistry method. Sections taken by vibratome from brain tissues of female rats were evaluated for the presence and density of glutamate receptor subunits in hypothalamic neurons. It was determined that the AMPA receptors subunits GluA1 and GluA2 are highly expressed in the hypothalamus while the synthesis of GluA3 and GluA4 is too limited. Very high number of GluK5-immunoreactive neurons was detected, where the expression of GluK1/2/3 was moderate. GluN1A, one of the NMDA receptor subunits, was found to be densely localized in the hypothalamus. In conclusion, with this study, many hypothalamic neurons can express ion-specific iGluR channels in different amounts and intensities, which would allow a differential regulation of the target neurons by glutamate.

Keywords

• Glutamate
• Kainic Acid
• AMPA
• NMDA
• Hypothalamus

Hipotalamusta İyonotropik Glutamat Reseptör Ekspresyonu: İmmunohistokimyasal Lokalizasyon Çalışması

Abstract

Merkezi sinir sisteminde (MSS) nöron fonksiyonlarının düzenlenmesinde çok çeşitli nörotransmitter madde rol oynar. Glutamat, hipotalamusta en önemli eksitatör amino asit nörotransmitterlerden biri olarak yer alır ve nöronlar üzerindeki düzenleyici işlevini iyonotropik ve metabotropik olarak iki alt ailede sınıflandırılan reseptörlerine bağlanarak gerçekleştirir. Glutamatın bazı nöroendokrin nöronlar üzerinde etkili olduğu yapılan elektrofizyolojik ve farmakolojik çalışmalarla belirlenmiştir. Çalışmamız kapsamında, glutamaterjik innervasyonun histomorfolojik olarak desteklendiği çalışmaların bulunmaması sebebiyle hipotalamik glutamat reseptör alt birimlerine odaklanılmıştır. İyonotropik glutamat reseptör alt birimlerinden AMPA (GluA1, GluA2, GluA3, GluA4), Kainik asit (GluK5, GluK1, GluK2, GluK3) ve NMDA’nın (GluN1, GluN2A) hipotalamustaki dağılımları immünohistokimya yöntemi kullanılarak araştırılmıştır. Dişi sıçanların beyin dokularından vibratom aracılığıyla alınan kesitler, hipotalamik nöronlardaki glutamat reseptör alt birimlerinin varlığı ve yoğunluğu açısından değerlendirilmiştir. Çalışmada, AMPA reseptörlerinden GluA1 ve GluA2’nin yaygın olarak hipotalamusta lokalize olduğu, GluA3 ve GluA4 immünoreaksiyonunun ise çok sınırlı olduğu; kainat reseptör alt birimlerinden GluK5’in çok yaygın olduğu ve GluK1/2/3 içeren nöronların daha az sayıda olduğu, NMDA reseptör alt birimlerinden GluN1’in ise hipotalamusta yoğun olarak bulunduğu saptanmıştır. Sonuç olarak, bu çalışma ile hipotalamik birçok nöronun iyon spesifik iGluR kanallarını farklı miktar ve yoğunlukta eksprese edebildiği, bunun da hedef nöronların glutamat tarafından farklı şekilde düzenlenmesine izin verebileceği gösterilmiştir.

Keywords

• Glutamat
• Kainik Asit
• AMPA
• NMDA
• Hipotalamus

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