Neuroinflammation and Synaptic Sensitization Mediated by Microglia and Astrocytes in Autism Spectrum Disorder

Yıl 2024, Cilt: 1 Sayı: 1, 46 - 60, 30.07.2024

Dursun Alper Yılmaz , İbrahim Hakkı Çağıran

Öz

Autism spectrum disorder (ASD) is recognized as a common neurodevelopmental disorder that begins in childhood. The pathophysiological basis of ASD has not yet been fully elucidated. Recently, there has been a growing interest in the effects of microglial and astrocytic cellular components in ASD. While microglial cells can modulate the morphological and functional integrity of the neuronal network by regulating synaptic connections, they can also respond to injury or pathogenic stimuli by secreting inflammatory cytokines that surround the site of injury. Similarly, astrocytes maintain homeostatic balance in the brain microenvironment through ion and neurotransmitter uptake. However, the molecular interactions between ASD and microglial and astrocytic cells are still poorly understood. Previous studies have demonstrated the presence of increased numbers of reactive microglia and astrocytes in postmortem tissue samples of ASD patients and in animals modeled for ASD, suggesting that microglia and astrocytes may play an important role in the pathogenesis of ASD. Therefore, a deeper understanding of the role of microglial and astrocytic influences in ASD is crucial for the development of effective therapeutic approaches. This review aims to examine microglial and astrocytic functions and their contribution to the pathogenesis of ASD.

Anahtar Kelimeler

Astrocytes, Microglia, Neuroinflammation, Autism spectrum disorder

Otizm Spektrum Bozukluğunda Mikroglia ve Astrositler Tarafından Aracılık Edilen Nöroinflamasyon ve Sinaptik Hassasiyet

Öz

Otizm spektrum bozukluğu (OSB), çocukluk döneminde başlayan ve yaygın bir nörogelişimsel bozukluk olarak kabul edilmektedir. OSB'nin patofizyolojik temelleri henüz tam olarak aydınlatılamamıştır. Yakın dönemde, OSB'deki mikroglial ve astrositik hücresel bileşenlerin etkilerine dair artan bir ilgi gözlemlenmektedir. Mikroglial hücreler, sinaptik bağlantıları düzenleyerek nöronal ağın morfolojik ve fonksiyonel bütünlüğünü modüle edebilirken, yaralanma veya patojenik uyarıcılara yanıt olarak yaralanma bölgesini saran inflamatuar sitokinlerin sekresyonunu gerçekleştirerek tepki verebilirler. Benzer şekilde, astrositler, iyon ve nörotransmitter alımı yoluyla beyin mikroçevresinde homeostatik dengeyi sağlamaktadır. Ancak, OSB ile mikroglial ve astrositik hücreler arasındaki moleküler etkileşimler hala tam olarak anlaşılmamıştır. Geçmiş çalışmalar, OSB hastalarının ölü doku örneklerinde ve OSB modellemesi yapılan hayvanlarda artmış sayıda reaktif mikroglia ve astrositin varlığına dair bulgular sunmuş, böylece mikroglia ve astrositlerin OSB'nin patogenezinde önemli bir role sahip olabileceği öne sürülmüştür. Dolayısıyla, mikroglial ve astrositik etkilerin OSB'deki rollerinin daha derinlemesine anlaşılması, etkili terapötik yaklaşımların geliştirilmesi açısından büyük bir öneme sahiptir. Bu derleme çalışması, mikroglial ve astrositik işlevleri ile OSB'nin patogeneza olan katkılarını incelemeyi hedeflemektedir.

Anahtar Kelimeler

Astrosit, Mikroglia, Nöroinflamasyon, Otizm spektrum bozukluğu

Kaynakça

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